Depola izing
Response
o
Ra
Pa a hy oid
Cells
o
Di alen
Ca ions
JOSE
LOPEZ-BARNEO
and
CLAY
M
.
ARMSTRONG
F om
he
Depa men
o
Physiology,
Uni e si y
o
Pennsyl ania
Medical
School,
Philadelphia,
Pennsyl ania
19104
ABSTRACT
Memb ane
po en ials
we e
eco ded
om
a
pa a hy oid
glands
con inuously pe used
in
i o
.
A
1
.5
mM
ex e nal
Ca",
he
es ing
po en ial
a e ages
-73
±
5
mV
(mean
±
SD,
n
=
66)
.
On
exposu e
o
2
.5
mM
Ca",
he
cells
depola ize
e e sibly
o a
po en ial
o
-34
±
8
mV
(mean
±
SD)
.
Depola iza ion
o
his
alue
is
comple e
in
^-2-4
min,
and
epola iza ion
on
e u n
o
1
.5
mM
Ca"
akes
abou
he
same
ime
.
The
depola izing
ac ion
o
high
Ca"
is
mimicked
by
all
di alen
ca ions
es ed,
wi h
he
ollowing
o de
o
e ec i eness
:
Ca"
>
S "
>
Mg"
>
Ba++
o
alkali-ea h
me als,
and
Ca"
>
Cd
++
>
Mn++
>
Co'
>
Zn
++
o
ansi ion
me als
.
Inpu
esis ance
in
1
.5
mM
Ca"
was
24
.35
±
14
MQ
(mean
±
SD)
and
inc eased
by
an
a e age
ac o
o
2
.43
±
0
.8
a e
swi ching
o
2
.5
mM
Ca++
.
The
low
alue
o
inpu
esis ance
sugges s
ha
cells
a e
coupled
by
low- esis ance
junc ions
.
The
es ing
po en ial
in
low
Ca'
is
qui e
insensi i e
o
emo al
o
ex e nal
Na
+
o Cl
-
,
bu
e y
sensi i e
o
changes
in
ex e nal
K+
.
Cells
depola ize
by 61
mV
o a
10= old
inc ease
in
ex e nal
K+
.
In
high
Ca
+
+,
memb ane
po en ial
is
less
sensi i e
o
an
inc ease
in
ex e nal
K+
and
is
unchanged
by
inc easing
K+
om
5 o
25
mM
.
Depola iza ion
e oked
by
high
Ca'
may
be
slowed,
bu
is
unchanged
in
ampli ude
by
emo al
o
ex e nal
Na+
o
Cl
-
.
O ganic
(13600)
and
ino ganic
(Co++,
Cd
++
,
and
Mn++)
blocke s
o
he
Ca'
channels
do
no
in e e e
wi h
he
elec ical
esponse
o
Ca"
changes
.
Ou
esul s
show
ema kable
pa allels
o
p e ious
obse -
a ions
on
he
con ol
o
pa a ho mone
(PTH)
elease
by
Ca"
.
They
sugges
an
associa ion
be ween
memb ane
ol age
and
sec e ion
ha
is
e y
unusual
:
pa a hy oid
cells
sec e e
when
ully
pola ized,
and
sec e e
less
when
depo-
la ized
.
The
ex ao dina y
sensi i i y
o
pa a hy oid
cells
o
di alen
ca ions
leads us
o
hypo hesize
he
exis ence
in
hei
memb anes
o
a
di alen
ca ion
ecep o
ha
con ols
memb ane
pe meabili y
(possibly
o
K
+
)
and
PTH
sec e ion
.
INTRODUCTION
I is
well
known
ha
he
a e
o
pa a hy oid
ho mone
sec e ion
(PTH)
is
in e sely
ela ed
o
se um
Ca
++
le els
.
In i o
(Maye
and
Hu s ,
1978
;
Add ess
ep in s
o
Clay
M
.
A ms ong,
Dep
.
o
Physiology,
G4,
.
Uni e si y
o
Pennsyl-
ania
School o
Medicine,
Philadelphia,
PA
19104
.
D
.
Lopez-Ba neo's
p esen add ess
is
Depa amen o
de
Fisiologia,
Facul ad
de
Medicina,
Se illa
9,
Spain
.
J
.
GEN
.
PHYSIOL
.
©The
Rocke elle Uni e si y
P ess
-
0022-1295/83/08/0269/26
$1
.00

269
Volume
82

Augus
1983

269-294
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270

THE
JOURNAL
OF GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
Pa
and
Luckha d , 1942)
and
in
i o
(B own
e al
.,
1976
;
Mo issey
and
Cohn,
1978
;
She wood
e
al
.,
1970) expe imen s
ha e
demons a ed
ha
a
sligh
dec ease
(on he
o de
o
en hs
o
millimoles)
in
ex e nal
Ca"
concen a ion
e okes
a
s ong
sec e o y
esponse
om
pa a hy oid
cells
.
Con e sely,
an
inc ease
in
ex acellula
Ca"
educes
he
a e
o
PTH
sec e ion
.
The
cu e
ela ing
sec e ion
o
Ca"
concen a ion
is
e y
s eep,
wi h
he
ull
sec e ion
a e
a
0-0
.5
mM
and
maximal
sup-
p ession
a
2-2
.5
mM
(B own
e
al
.,
1976
;
Habene
and
Po s,
1976
;
Mo issey
and Cohn,
1978)
.
The
s eepness
o
he
cu e
sugges s
he
exis ence
in
pa a hy oid
cells
o an
unusual
and
e y
sensi i e
Ca-sensing
mechanism,
he
na u e
o
which
has
no
been
disco e ed
.
In
many
sec e o y
cells,
ex e nal
Ca"
is
essen ial
o
sec e ion
.
Phys-
iological
s imula ion
esul s
in
Ca"
en y
in o
he
cell
in e io ,
which
is
esponsible o igge ing
exocy osis
(Douglas,
1968
;
Pe e sen,
1980
;
Rubin,
1970)
.
This
gene al
scheme
may
no
apply
o
pa a hy oid
cells
.
An
inc ease
in
ex e nal
Ca",
as
well
as
Mg",
dec eases
PTH
sec e ion
(B own
e
al
.,
1976
;
Habene and
Po s,
1976
;
She wood
e
al
.,
1970)
and
ull
sec e o y
ac i i y
can
be
obse ed
in
he
absence
o
ex e nal
Ca"
(Fische
e
al
.,
1982
;
Pin ado
and
Wallace, pe sonal
communica ion)
.
In
addi ion,
applica ion
o
he
calcium
ionopho e
A23187,
which
p esum-
ably
inc eases
cy osolic
Ca"
(Reed
and
La dy,
1972),
inhibi s
PTH
sec e ion
(B own
e
al
.,
1980
;
Fische
e
al
.,
1982
;
Habene
e
al
.,
1977)
.
Memb ane
elec ical
ac i i y
plays
an
impo an
ole
in
s imulus-sec e-
ion
coupling
in
many
gland
cells
(Pe e sen,
1980)
.
Elec ophysiological
s udies
on
he
pa a hy oid
ha e
been
pe o med
only
ecen ly
and
he
wo
epo s
a ailable
show
con adic o y
indings
.
In
mouse
pa a hy oid
gland,
in
i o in acellula
eco dings
by
B uce
and Ande son
(1979)
show
ha
cells
hype pola ize
when
he
ex e nal
Ca"
concen a ion
dec eases
.
In
con as ,
i
has
been
epo ed
ha
goa pa a hy oid
cells
main ained
in
cul u e
depola ize
in
low
Ca"
and
ha
ol age-dependen
Ca"
en y
may
igge
PTH
exocy osis
(Sand
e
al
.,
1981)
.
We
ha e
pe o med
expe imen s
in
a
pa a hy oid glands
in
i o
and
ha e
ound
a
e y
clea
and
e e sible
depola iza ion
in
esponse
o
inc eased
ex e nal
Ca"
in
he
physiological
ange
o
a s
(Ro h
and
Raisz,
1964)
.
Ou
esul s
hus
ag ee
quali a i ely
wi h
hose
ound
in
he
mouse
(B uce
and
Ande son,
1979)
.
Depola iza ion
is
also
obse ed
a e
addi ion
o
all
di alen
ca ions
es ed,
bo h
alkali-ea h
and
ansi ion
me als,
including
he
Ca"
channel
blocke s
Cd",
Mn",
and
Co"
.
The
depola iza ion
e oked
by
inc eased
Ca"
is
accompanied
by
an
inc ease
in
inpu
esis ance
and
may
be
due
o a
supp ession
o
K+
pe meabili y
.
The
possibili y
ha
a
di alen
ca ion
ecep o
loca ed
on
he
ex e nal
su ace
o
he
memb ane
con ols
memb ane
pe meabili y
and,
in
u n,
PTH
sec e ion,
is
conside ed
.
METHODS
P epa a ion
Expe imen s
we e
pe o med
on
pa a hy oid
glands
ob ained
om
adul ,
male
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LOPEZ-BARNEO
AND
ARMSTRONG
Depola izing
Response
o
Ra
Pa a hy oid
Cells

271
Wis a
a s
100-200
g
in
weigh
.
Animals
we e
killed
wi h
e he
and
he
gland
was
excised
unde a
dissec ing
mic oscope
.
Pa a hy oid
glands
in
he
a
a e
loca ed
bila e ally
in
he
la e al
bo de
o
he
hy oid
gland
and
appea
as
pale
o oids
-
1-1
.5
mm
in
diame e
pa ially
embedded
in
he
hy oid
issue
(G eene,
1935)
.
The
pa a hy oid gland
and
pa
o
he
hy oid
issue
adjacen
o
i
we e
ans e ed
o
he eco ding
chambe
and
secu ed
o
he
bo om
by
small
s ainless-s eel
pins
.
The
hin
connec i e
capsule
co e ing
he
gland
was
emo ed
wi h
he aid
o
a
s e eomic oscope
.
Expe imen al
Se up
The
eco ding
chambe
and
pa o
he expe imen al
se up
a e
schema ically
ep esen ed
in
Fig
.
1
.
The
chambe
was
made
o
luci e
and
di ided
in o
h ee
3 2
FIGURE
1
.
Schema ic
d awing
o
he
appa a us
used
o
in acellula
eco ding
in
he
con inuously
pe used
pa a hy oid
gland
. 1
:
eco ding
chambe
.
2
:
in e media e
ese oi
.
3
:
ese oi
whe e
he
suc ion
(5)
is
applied
.
Fluid lows
be ween
1,
2,
and
3
by
way
o
co on
wicks
.
4
:
s opcock
o selec
be ween
i e
di e en solu ions
.
6
:
mic o he mis o
pe manen ly
a ached
o
he
eco ding
chambe
.
7
:
hea ing
ilamen
ha
wa ms
up
he
in low
solu ion
.
8
:
glass
mic oelec ode
.
9
:
3
M
KC1
aga
b idge
.
10
:
ol age
ollowe
.
11
:
s age o
elec onic
compensa ion
o
elec ode capaci ance
and
esis ance
.
12
:
squa e
cu en
pulses
(ob ained
om a
cons an
cu en
pump)
ha
can
be
injec ed
h ough
he mic oelec ode
.
compa men s
.
The
gland
was
placed
in
he
i s
compa men
(1),
si ing
on
a
laye o
Sylga d
(Dow
Co ning
Co p
.,
Midland,
MI)
.
This
compa men
con-
ained
he
inle
o
he
ex e nal
luid
.
A
hin
wall
o
plas ic
a ached
o
he
bo om
o
he
chambe
(no
illus a ed
in
he
igu e)
was
placed
as
a
ba le
be ween
he
gland
and
he
inle
ape u e
o
di ec
he
solu ion
s eam
away om
he mic oelec ode
.
The
eco ding
compa men had a
olume
o
-0
.5
cm' and
he
ba hing
solu ion
low
a e
was
1
ml/min
.
Solu ion
lowed
om
compa men
1
o
a
bu e
compa men
(2)
and
om
his
o
a
hi d
compa men
(3),
whe e
suc ion
was
applied
.
Flow
be ween
compa men s
was
by
way
o
co on
wicks
.
A
silk
h ead
glued
a
he
ou le
needle
(5)
was
used
o
b eak
he
meniscus,
making
he
suc ion
egula
and
smoo h
.
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27
2

THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
The
ex e nal
pe usion sys em
was
moun ed
sepa a ely
om
he
eco ding
able
.
Any
one
o
i e
solu ions
could
be
applied
while
eco ding
in
a
gi en
pa a hy oid
cell
.
Swi ching
was accomplished
wi hou
in e up ing
he
solu ion
low,
and
he
le el
o
solu ion
in
he
eco ding
compa men
was
hus
kep
cons an
.
The
dead
space
o
he pe usion
sys em
was
<0
.1
ml
and
i s
washou
ime was
1
o
2
s
.
The
empe a u e
in
he
eco ding
compa men
was
moni o ed
wi h
a
mic o he mis o
(6)
and
con olled
by a
ci cui
o
ou
own
design
.
This
ci cui
passed he
app op ia e cu en
h ough
a
coil
(7)
placed
a ound
he
solu ion
inle ,
hus
main aining
he
eco ding
compa men
a
37°C
.
Solu ions
Solu ion
composi ions
a e
shown
in
Table
I
.
Modi ied
K ebs
solu ions
wi h
a iable
Ca"
concen a ions
(be ween 0
.5
and
2
.5
mM)
we e
made
by
mixing
solu ions
A
and
B
.
In
expe imen s
whe e
he
e ec s
o
di alen
ca ions
o he
han
Ca"
o
Mg"
we e
es ed,
S C1
2
,
BaC1
2
,
MnC1
2
,
CdC1
2
,
COC1
2
,
o
ZnCl
2
we e
subs i u ed
equimola ly
o
NaCl
.
Cl- ee
solu ions
(98%
Cl- ee)
wi h
a iable
K'
concen a ions
we e
made
by mixing
solu ions
E, F,
G,
and
H
.
In
Reco ding
TABLE
I
Composi ion
o
Solu ions
(in
mM)
some
expe imen s
a iable
amoun s
o
D600
om
a
I-mM
s ock
solu ion
we e
added
o
he
modi ied
K ebs
solu ion
un il
eaching
inal
concen a ions
be ween
30
and
150
uM
.
The
pH
o
all
solu ions
was
adjus ed
o
7
.4
excep
o
he
Na-
ee
solu ions
(C
and
D),
whe e
T izma,
pH
7
.5,
was used
as
bu e
and
as
Na
subs i u e
.
Solu ions
we e
con inuously
bubbled
wi h
100%
02
and had
an
osmolali y
o
270-290
mosmol/kg
.
The
junc ion
po en ials
o
all
solu ions
we e
measu ed
wi h
he
elec ode
placed
in
he
eco ding
chambe
.
In
solu ions
wi h
di e ences
only
in
di alen
ca ion
concen a ion,
he
junc ion
po en ial
di e ed
by
<1
mV
.
When
swi ching
om
a
modi ied
K ebs
solu ion
o a
Na- ee
solu ion,
a
junc ion
po en ial
o
+4
mV
was obse ed
.
Pa a hy oid
cells
we e
impaled
wi h
glass
mic oelec odes
illed
wi h
3
M
KCl
and
ha ing
100-200
MQ
DC
esis ance
.
The
mic oelec odes
we e
pulled
wi h
a
e ical
pulle
om
hick-walled
bo osilica e
glass
(OD
=
2
mm,
ID
=
0
.7
mm)
wi h
an
inne ilamen
o
ease
o
illing
.
The
mic oelec odes
we e
elec ically
connec ed
o
an
FET
ope a ional
ampli ie
(AD515
;
Analog
De ices,
Inc
.,
A
K ebs
0
.5
Ca
B
K ebs
2
.5
Ca
C
Na- ee
1
.5
Ca
D
Na- ee
2
.5
Ca
E
CI- ee,
0K,2Ca
F
Cl- ee,
0K,4Ca
G
CI- ee,
100
K,
2
Ca
H
CI- ee,
100 K,
4
Ca
NaCl
120
117
- -
-
---
KCI
5
5
5 5
- - - -
K-glu ama e
- - - - -
-
100 100
Na- uma a e
2
.7
2
.7
-
-
2
.7
2
.7
2
.7
2
.7
Na-py u a e
4
.9
4
.9
- -
4
.9
4
.9
4
.9
4
.9
Na-glu ama e
4
.9
4
.9
- -
130
127
30
27
MgS0
4
1
.1
1
.1
1
.1
1
.1
1
.1
1
.1
1
.1
1
.1
CaC12
0
.5
2
.5
1
.5
2
.5
2
.0
4
.0
2
.0
4
.0
Glucose
2
.8
2
.8
2
.8
2
.8
2
.8
2
.8
2
.8
2
.8
HEPES
10
10
-
-
10 10 10
10
T izma
(pH
7
.5)
- -
142
.5
141
.5
-
- -
-
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LUPEz-BARNEO
AND
ARMSTRONG

Depola izing
Response o
Ra
Pa a hy oid
Cells

273
No wood,
MA)
wi ed
as
a
ol age ollowe
and
placed
close
o
he
p epa a ion
.
Ex e nal
ol age
was
sensed
by
a 3
M
KCl
aga
b idge
placed
in
he
eco ding
compa men
o
he
chambe
.
The
memb ane
po en ial
was
simul aneously
moni o ed
by an
oscilloscope
and
a
digi al
me e ,
and
eco ded
on
a
cha
eco de
(B ush
Ins umen s,
Gould
Inc
.,
Cle eland,
OH)
wi h
a
equency
esponse
o
^
"
100
Hz
.
Squa e
pulses
o
200
ms
du a ion
and
a iable
ampli ude
(be ween
0
.1
and 0
.25
nA)
ob ained
om
a
cons an -cu en
pump
we e
injec ed
h ough
he mic oelec ode
o
measu e
inpu
esis ance
.
S ay capaci ance
and
ol age
d op
ac oss he
mic oelec ode
we e
elec onically
compensa ed
.
The
eco ding
chambe
and
mic omanipula o
we e
placed
on
a
hea y
g ani e
able
si ing
on
inne ubes
o
shock
abso p ion
.
The
eco ding
able
was
elec ically
shielded
o
p e en
noise
.
Expe imen al
P ocedu e
Cells
we e
success ully
impaled
as
deep
as
250-300
jm
om
he
su ace
o
he
gland
.
Mos impalemen s
only
las ed
o
a
ew
seconds,
bu
occasionally
he
elec ode
s ayed
in
he
cell
and
a
s able
alue
o
he
memb ane
po en ial
was
eached
in
2
o
3
min
.
Good
impalemen s
we e
cha ac e ized
by
a
sudden change
in
he
memb ane
po en ial
.
In
all
cases,
he
eco ded
ol age
was
balanced
o
ze o
be o e
en e ing
he
gland
.
A e
an
impalemen ,
a
check
o ol age
d i
was
made
by
wi hd awing
he
elec ode
om
he
gland
.
In
e e y
cell
om
which
a
s able
eco ding
could
be
made,
he
esponse
o
changes
in
ex e nal
Ca"
concen a ion
was
es ed
.
This
was
used
as
an
indica ion
ha
he
eco dings
we e
made
in
a
quali a i ely
homogeneous
popula ion
o
pa a hy oid
cells
.
A e
his
es ,
he
es
o
he
expe imen al
p o ocol
was
pe o med
.
We
ha e eco ded
mo e
han
60
pa a hy oid
cells
o
pe iods
om
10
min
o
>3
h
.
In
long
pene a ions
i
was
possible
o
es
se e al
solu ions
wi h
di e en
ionic
compo-
si ions
.
In
many
o he
cells,
s able
eco dings
las ing
se e al
minu es
we e
ob ained,
bu he
elec ode
came
ou
o
he
cell
be o e
a
solu ion
change
could
be
accomplished
.
RESULTS
Res ing
Po en ial
in
Pa a hy oid
Cells
Mos
cells
we e
impaled
while
he
gland
was
ba hed
wi h
a
solu ion
con aining
1
.5
mM
Ca"
.
In
many
o
hese
cells,
he
es ing
po en ial
s abilized in
he
i s
minu e
a e
he
pene a ion,
eaching
an
a e age
alue
o
-73
±
5
mV
(mean
±
SD,
n
=
66)
.
Memb ane
Po en ial
Depends
on
Ex e nal
Ca
In
all
pa a hy oid
cells
exposed
o
mo e
han
one
solu ion,
he
magni ude
o
he
memb ane
po en ial
was
s ongly
dependen
on
he
concen a ion
o
ex e nal
Ca"
.
This
is
illus a ed in
Fig
.
2
by
a
con inuous
eco ding
o
memb ane
ol age
om
a
single
cell
.
The
cell
was
ini ially
impaled
in
K ebs
2
.5
mM
Ca",
yielding
a
es ing
po en ial
o
-27
mV
.
Solu ion
changes
a e
indica ed
by
he
a ows
.
The
eco ds
show
e y
clea ly
ha
memb ane
po en ial
depends
s ongly
and
e e sibly
on
ex e nal
Ca"
.
The
cell
depola izes
in
esponse
o
an
inc ease
in
ex e nal
Ca"
a e
a
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983

27
4
memb o~e
po en ial
(mV)

elec ode
in,
2
.5mMCa
"
I
-
I
-257
-50
7
-75-~
THE
JOURNAL
OF GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
delay
equi ed
o
washou
and
equilib a ion
.
Once
he
memb ane
po en-
ial
s a ed
o
change,
he
ime equi ed
o a ain
he
new
s eady
s a e
le el
was
be ween
1
.5
and
3
min,
depending
on
each
pa icula
cell
.
Memb ane
ol age
is
sensi i e o
ex e nal
Ca"
in
a
na ow
concen a-
ion
ange,
be ween
1
and
2
.5
mM
Ca"
.
Ca"
concen a ions
o
<1
mM
we e
only
es ed
in
a ew
cells
because,
o
unknown
easons,
pe haps
chance,
i
was
di icul
o ob ain
s able
in acellula
eco dings
.
In
he
lowe
pa
o
Fig
.
2,
swi ching
om
1
.5
o
0
.5
mM
Ca"
solu ion
does
0-
-25-
_50-
-75-
-100i

2
5Co

1
SCa

0
5Ca

2
.5Co
5min
FIGURE
2
.

Modi ica ions
o
memb ane
po en ial
by
changes
o ex e nal
Ca"
concen a ion
.
The
aces
a e
a
con inuous
in acellula
eco ding
om
a
pa a hy oid
cell
exposed
o
di e en
ex e nal
Ca"
concen a ions
a
he
ime
indica ed
.
The
cell
was
impaled
in
a
solu ion
con aining
2
.5
mM
Ca"
.
The
s eepes
ol age
esponse
occu s
be ween
1
.5
and
2
.5
mM
Ca"
.
In
0
.5
mM
Ca
+,
he
memb ane
po en ial
is
abou
he
same
as in
1
.5
mM
Ca",
o
sligh ly
mo e
posi i e
.
Di e en
Ca"
concen a ions
we e
ob ained
by
mixing
solu ions
A
and
B
o
Table
1
.
Osmolali y
o
all
solu ions
was
be ween
270 and 290
mosmol/kg,
pH
7
.4,
empe a u e
37°C
.
no
ha e an
app eciable
e ec
on
he
memb ane
po en ial
.
Some
cells
e en
showed
a
sligh
depola iza ion
when
he
ba hing
solu ion
was
changed
om
1
.5
o
0
.5
mM
Ca"
.
The
mean
es ing
po en ial
o
se e al
cells
as
a
unc ion
o
ex e nal
Ca"
concen a ion
is
shown
in
Fig
.
3
.
The
alues
in
A
a e
om
cells
con inuously
eco ded
o
10-120
min
and
exposed
o
a
leas
wo
solu ions
wi h
di e en
Ca"
concen a ions
.
Ex eme
alues
o
po en ial
we e
-34
±
8
mV
(mean
±
SD)
in
2
.5
mM
Ca"
and
-80
.5
±
2
mV
(mean
±
SD)
in
1
.0
mM
Ca"
.
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
LOPEZ-BARNEO
AND
ARMSTRONG
Depola izing
Response o
Ra
Pa a hy oid
Cells

275
Fig
.
3B
shows
he
same
cu e
compiled
om
pene a ions
main ained
o
only
1-10
min,
oo
sho
a
ime
o a
solu ion
change
o
be
accom-
plished
.
The
Ca"
concen a ion
in
he
ba hing
solu ion
o
each
pene a-
ion
is
gi en
on
he
axis
.
The
measu emen s
by
he
wo
me hods
a e
in
excellen
ag eemen
and
clea l~
demons a e
ha
in
pa a hy oid
cells
a
1
.5
mM
change
in
ex e nal
Ca
+
in
a
de ini e
ange
(be ween
1
and
2
.5
mM)
e okes
a
mean
po en ial
change
o
46
mV
.
The
ela ionship
be ween
memb ane
po en ial
and
ex e nal
Ca"
in
ha
ange
is
e y
s eep
.
One
o
he
mos
s iking
cha ac e is ics
o
his
elec ical
esponse
is
i s
nea ly
pe ec
e e sibili y
.
Some
cells
we e
exposed
se e al
imes o
A
_20-
.
30-
.40-
.
50-
.W
-70
-80
mamb
po en ial
W

g

al
jm l
0

0-
.
10
i

-1
_20-
.
30-
.40-

1101
-50J 131
-6
-70
.
80
131
1341
QS

1

5
2
2S
(Ca-1

OS

1

1
.5

2
2
.51Ca**I
FIGURE
3
.

Memb ane
po en ial
in
pa a hy oid
cells
as
a
unc ion
o
ex-
e nal
Ca"
.
(A)
Da a
om
single
pene a ions
ha
we e
held long
enough
(10
min
o
3
h)
o
eco d
es ing
po en ial
in a
leas
h ee
solu ions
wi h
di e en
Ca"
concen a ions
.
Each
poin ep esen s
he
mean
±
SD
o 3-
27
measu emen s
as
gi en
by
he
numbe s
in
pa en heses
.
(B)
Da a
om
pene a ions
oo
b ie
o
allow
a
chan e
o
he
ba hing
solu ion
.
The
pene a ions
we e pe o med
in
he
Ca
'
concen a ion
speci ied
on
he
axis,
and
he
es ing
po en ial
emained
s able
o
1-10
min
.
Each
poin
ep esen s
he
mean
±
SD
o
1-66
measu emen s,
and
he
numbe s
o
measu emen s
a e
in
pa en heses
.
Composi ion
o
solu ions
is
he
same
as
in
Fig
.
2
.
solu ions
wi h
1
.5
and
2
.5
mM
Ca"
and
he
memb ane
po en ial
was
measu ed
a
a
gi en
ime
a e
he
solu ion
change
.
In a
ypical
cell
he
mean
memb ane
po en ial
alues
o
eigh
measu emen s
done 5-6 min
a e
swi ch4
o
he
new
solu ion
we e
-79
.7
±
2
.4
mV
(mean
±
SD)
in
1
.5
mM
Ca
+
and
-32
.2
±
2
.5
mV
(mean
±
SD)
in
2
.5
mM
Ca"
.
The
ex emely
small
dispe sion
a ound
he
mean
indica es
a nea ly pe ec
e e sibili y
o
he
esponse
.
On
h ee
occasions
s able in acellula
eco dings
om
he
issue su -
ounding
he
pa a hy oid
gland
(p esumably
om
hy oid
cells)
we e
ob ained
.
The
es ing
po en ial
o
hese
cells
was
abou
-65
mV
and
did
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
276

THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
no
show
any
app eciable
modi ica ion
in
esponse
o
changes
in
ex e nal
Ca"
concen a ion
in
he
ange o 0
.5-2
.5
mM
Ca"
.
Absence o
Spike
Ac i i y
The
elec ical
esponse
e oked
by
inc easing
o
dec easing
ex e nal
Ca"
always
showed
he
quali a i e
ea u es
e e ed
o
abo e
and
no
spiking
ac i i y
was
e e seen
.
In
some
cells
ha
showed
a
e y
low
es ing
po en ial
(-40
mV
in
1
.5
mM
Ca"),
i egula
jumps
and
spikes
we e
obse ed
in
he
i s
seconds
a e
he
impalemen
ha
we e
p obably
due
o
an
impe ec
pene a ion
o
he
cell,
since
ei he
he
mic oelec ode
came
ou o
he
cell
sho ly
a e
he
impalemen
o
he
memb ane
sealed
a ound
he
elec ode
and
he
"spikes"
disappea ed
as
memb ane
po en ial
inc eased
.
Calcium
E ec s
A e
Mimicked
by
O he
Di alen
Ca ions
O he
alkali-ea h
ca ions
ha e
he
same
quali a i e
e ec
on
pa a hy oid
cell
memb ane
po en ial
as
Ca"
.
This
is
illus a ed
in
Fig
.
4A,
which
shows
a
con inuous
in acellula
eco ding
om
a
single
cell
.
The
ini ial
impalemen
was
done
in
a
solu ion
con aining
1
.5
mM
Ca",
yielding
a
es ing
po en ial
o
-76
mV
.
A
he
ime
indica ed
by
he
a ows,
he
ba hing
solu ion
was
changed
o
one
con aining,
in
addi ion
o
1
.5
mM
Ca",
1
mM
o
ano he
di alen
ca ion
.
All
he
ca ions
caused
a
e e sible
depola iza ion,
bu
wi h
di e en
ime
cou ses
and
magni udes
.
The
e ec i eness
o
he
esponse
was
Ca'
>
S ++
>
Mg++
>
Ba++
.
None
o
hese
di alen
ca ions
was
as
e ec i e
as
Ca++
in
depola izing
pa a hy oid
cells
.
S
++
and
Ba
++
esponses
we e,
espec i ely,
^-60
and
^-30%
o
he
depola iza ion
obse ed
wi h
Ca
++
.
Mg
+
yielded
an
in e media e
alue
.
The
di e ence
in
he
ime
cou se
is
also
e y
appa en
.
Whe eas
he
depola iza ion
induced
by
1
mM
addi ional
Ca
++
eached
he
s eady
s a e
in
2
.5
min,
he
Ba
++
-induced
depola iza ion
was
h ee imes smalle
and
equi ed
^ 6
min
o
a ain
he
s eady
s a e
.
The
same
expe imen al
p o ocol
shown
in
Fig
.
4A
has
been
epea ed
in
h ee
di e en
cells
wi h
simila
esul s
.
We
ha e
also
s udied
he
e ec
o
o he
di alen
ca ions,
and
an
example
is
shown
in
Fig
.
4B
.
The
eco d
belongs
o
ano he
pa a hy oid
cell
impaled
in
1
.5
mM
Ca
++
,
wi h
an
ini ial
memb ane
po en ial
o
-75
mV
.
The
expe imen al
p o ocol
was
he
same
as
be o e
:
in
addi ion
o
1
.5
mM
Ca
+
,
1
mM
o a
es
di alen
ca ion
was
added
o
he
ba hing
solu ion
.
In
all
cases
he
cell
depola ized
when
he
es
ca ion
was
added
.
In
his
case
he
e ec i eness
o
he
esponse
is
Ca
++
>
Cd
++
>
Mn++
>
Co
++
.
Cd
++
and
Mn
++
seem
o
be
sligh ly
mo e
e ec i e
han
S
++
,
and
he
e ec i eness
o
Co
++
is
abou
he
same
as
wi h
Ba
++
.
The
e ec s
o
Cd
++
,
Mn
++
,
and
Co
++
ha e
been
es ed
in
wo
di e en
cells
wi h
iden ical
quali a i e
esul s
.
Zn
++
was
es ed
in
a
cell
(no
illus a ed)
and
e oked
a
depola iza ion
o
abou
he
same
magni ude
as
Co
++
.
Fig
.
4A
and
B
shows
unequi ocally
ha
memb ane
po en ial
in
pa a hy oid
cells
is
a ec ed
no
only
by
ex e nal
Ca
++
bu by
all
he
di alen
ca ions
es ed
.
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
LOPEz-BARNEO
AND
ARMSTRONG

Depola izing
Response
o
Ra
Pa a hy oid
Cells

277
Inpu
Resis ance
and
Cell- o-Cell
Coupling
Inpu
esis ance
has
been
measu ed
in
se e al
cells
by
passing
hype pola -
izing
squa e
cu en
pulses
h ough
he
eco ding
mic oelec ode
.
Fo
hese
measu emen s
he
ol age
d op
ac oss
he
mic oelec ode
esis ance
memb ape
po en
i
o
l
elec ode
in

(mV)
o,
_
.
1
.5mMCa+*
B
1mm
g
o
++
5 min



2
.5MM
1
.5nW
1
.5mm

1
.5mm
1
.5MM
1
.SMM
1
.5 nM
1
.5mm
Ca
++
Ca
++
co"
,
Ca+'
Ca
++
Ca
++
Ca+
+
C
a
'+
1mMCd
++
1mmco
++
1 nMMn++
5min
FIGURE
4
.

E ec
o
a ious
di alen ca ions
on
memb ane
po en ial
o
pa a hy oid
cells
.
A
shows
a
con inuous
in acellula
eco ding
om
a
cell
ba hed
wi h
solu ions
con aining
he
indica ed
concen a ion
o
di alen
ca ions
.
The
cell
was
impaled
in
1
.5
mM
Ca
++
,
and
swi ches o
o he
solu ions
a e
indica ed
by
he
a ows
.
Solu ion
composi ion
is
he
same
as
in
Fig
.
1,
excep
ha
MgC1
2
,
S Cl
2
,
BaC1
2
,
o
addi ional
CaC1
2
we e
subs i u ed
equimola ly
o
NaCl
.
The
dashed
ho izon al
line a
-50
mV
memb ane
po en ial
is
d awn
o
con enience
o
compa ison
.
B
shows
a
con inuous
eco ding
o
ano he
cell
exposed
o he
indica ed
ansi ion
elemen s
.
The
ime
be ween
he
pa allel
ba s in
he
eco d
was
2
.5
min,
and
he
dashed
line a
-57
mV
memb ane
po en ial
is
d awn
o
con en-
ience
.
was
sub ac ed
ou
elec onically
.
The
sub ac ion
ci cui
was
adjus ed
be o e
pene a ing
he
cell
;
he
adequacy
o
he
sub ac ion
was
es ed
a e
he elec ode
was wi hd awn
.
The
measu emen
was
disca ded
i
elec ode
esis ance
changed
signi ican ly
du ing
he pene a ion
.
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
28
4

THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
5
mM
K
+
solu ion,
he
cell
epola izes
o
app oxima ely
he
o iginal
le el
.
In
all
cells
depola ized
by
ele a ed ex e nal
K+, he
epola iza ion
showed
a
slowe
ime
cou se
han
he
depola iza ion
.
Fig
.
9A
also
shows
ha
he
same
cell
was
depola ized
e e sibly
by 4
mM
Ca"
a
a
cons an
(5
mM)
K+
concen a ion
by ^-36
mV
.
Fig
.
9B
illus a es
a
con inuous
in acellula
eco ding
om
ano he
cell,
which
was
ini ially
impaled
in
5
mM
K,
4
mM
Ca
and
had
a
es ing
po en ial
o
-33
mV
.
V
m
wen
nega i e
by 34
mV
on
changing
o
5
mM
K, 2
mM
Ca
.
The
addi ion o
25
mM
K,
2
mM
Ca
e e sibly
depola ized
he
cell
by
28
mV
.
A e
eco e y
in
5
mM
K,
2
mM
Ca,
he
cell
was
subsequen ly depola ized
by 43
mV
in
5
mM
K,
4
mM
Ca,
eaching
a
memb ane
po en ial
o
abou
-30
mV
.
A
his
poin
he
addi ion
o
25
and
50
mM
K+, keeping
cons an he
ex e nal
Ca",
had
li le, i
any,
e ec
on
he
memb ane
po en ial
.
The
ein oduc ion
o 5
mM
K, 2
mM
Ca
solu ion
epola ized he
cell
o
he
p e ious
es ing
po en ial
le el
(-74
mV)
.
Fig
.
9B
also
shows
ha
he ime
cou se
o
memb ane
depola -
iza ion
and
hype pola iza ion
induced
by
Ca"
is
e y
simila
o
he
ol age
changes obse ed by
he
in oduc ion
o
he
wi hd awal
o
high
K
+
solu ion
.
The
eco ds
in
Fig
.
9
a e
ypical
examples
o
he
esponse
o
pa a hy-
oid
cells
o
changes
in
ex e nal
Ca"
and
K'
in
Cl- ee
solu ions,
and
hey
sugges
ha
ex e nal Cl
-
does
no
make
an
impo an
con ibu ion
o
ei he
he
es ing
po en ial
o
he
Ca"-induced
elec ical
esponse
.
In
low
Ca",
he
memb ane
po en ial
is
highl~
sensi i e
o
ex e nal
K+,
bu
once
he
cells
a e
depola ized
by
high
Ca
',
ex e nal
K
+
seems
o
ha e
li le
e ec
on
he
memb ane
po en ial
.
The
e ec s
o ex e nal
Ca
+
and
K
+
in
Cl- ee
solu ions
ha e
been
s udied
in
many
cells
and
a
summa y
is
gi en
in
Fig
.
10
.
In
he
igu e,
memb ane
po en ial
in
2
mM
( illed
symbols)
and
4
mM
(open
symbols)
Ca"
has
been
plo ed
s
.
he
loga i hm
o
ex e nal
K+
.
The
e ical
line
ep esen s
he
s anda d
de ia ion
o
he
mean
and
he
numbe s
o
obse a ions
a e
in
pa en heses
.
In
low
Ca",
he
memb ane
po en ial
is
e y
sensi i e
o ex e nal
K+
.
Fi ing
by
eye,
he
s aigh
pa
o
he
cu e
(abo e
25
mM
K+)
yields
an
^-61
mV
change
in
memb ane
po en ial o
a
10- old
change
in
ex e nal
K
+
,
which
is
simila
o
he
alue
p edic ed
by
he
Ne ns
equa ion
o
a
po assium
elec ode
a
37'C
.
Ex apola ing
he
s aigh
line o
0
mV
memb ane
po en ial
gi es
an
es ima e
o
he
in acellula
po assium
concen a ion
o
160
mM
.
A
high
Ca",
he
numbe
o
measu emen s
is
smalle ,
bu
i
is
e y
clea
ha
memb ane
po en ial
is
less
sensi i e
o ex e nal
K+
.
Thus,
i
seems
ha
a
low
Ca",
pa a hy oid
cells
beha e
as
a
po assium
elec ode
and
P
K
is
he
dominan
pe meabili y
.
A
high
Ca",
he
a io
o
P
K
o
o he
pe meabili ies
p ob-
ably
dec eases
and
hus
memb ane
po en ial
is
less
sensi i e o
ex e nal
po assium
.
The
possible
pa icipa ion
o
di e en
ionic
pe meabili ies
in
he
ol age
change
seen
in
pa a hy oid
cells
will
be
analyzed
in
he
Discussion
.
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983

LOPEz-BARNEO
AND
ARMSTRONG
Depola izing
Response
o
Ra
Pa a hy oid
Cells

285
E ec s
o
Isop o e enol
I
is
known
ha
he
be a
agonis
isop o e enol,
a
concen a ions
be ween
1
and
10
gym,
inc eases
PTH
sec e ion
a e
in
dispe sed
bo ine
pa a hy-
oid
cells
(B own
e
al
.,
1977)
.
We
ha e
s udied
he
e ec s
o
a iable
concen a ions
o
isop o e enol
(be ween 10
and
40
uM)
added
o
he
modi ied
K ebs
solu ion
in
ou
cells
whose
elec ical
esponse
o
ex e nal
Ca"
had
p e iously
been
obse ed
.
These
concen a ions
o
isop o e -
enol
did no
ha e
an impo an
e ec
on
he
memb ane
po en ial ei he
a
low o
a
high
Ca"
.
In
one
cell
he e
was
no
ol age
change
a
all
.
In
ano he
cell
memb ane
po en ial
hype pola ized
by
6-7
mV,
and
in
he
memb ane
po en ial
InIVI
0-
--------------------------------------------------
-10-
-20-

/
.
a(l)
/ool
.~h)
b(3)
_40
(,3)

/
-
so
-
_60
-
-70
.
'
~
.
1(34)
-80
.

IF
5

10

25

50

100

160
mM
log
CKa7
FIGURE
10
.

Dependence
o
memb ane
po en ial
(o dina e)
on
he
ex e -
nal
concen a ion
o
K'
ep esen ed
in
a
semiloga i hmic
scale
(abscissa)
.
Filled
ci cles
a e
measu emen s
in
low
Ca"
(2
mM)
and
open
squa es
a e
measu emen s
in
high
Ca"
(4
mM)
.
E e y
poin
ep esen s
he
mean
and
he
e ical
ba s
ep esen
he
s anda d
de ia ion
o
se e al
measu emen s
ob ained
om
eco ds
like
hose
shown
in
Fig
.
10
.
The
numbe
o
meas-
u emen s
is
in
pa en heses
.
The
s aigh
line
has
been
d awn
by
eye
and
has
a
slope o
^-61
mV
pe
10- old inc ease
in
ex e nal
K+
concen a ion
.
The
in e cep
o
his line
wi h
he
0-mV
axis
gi es
an
es ima e
o
he
in e nal
concen a ion
o
K+
.
o he
wo
cases
a
4-5-mV
depola iza ion
was
obse ed
.
Al hough
he
numbe
o
obse a ions
is
small
and
no
de ini i e
conclusion
can
be
d awn,
ou
da a
sugges
ha
he
mechanism
o
isop o e enol
s imula ion
o
pa a hy oid
cells
is
di e en
om
ha
e oked
by
lowe ing
di alen
ca ions
(see
Discussion)
.
DISCUSSION
The
e ec s
o
ex e nal
calcium
concen a ion
on
pa a hy oid
cell
mem-
b ane
po en ial
ha e
been' epo ed
only
wice,
wi h
con adic o y
conclu-
sions
.
Mouse
pa a hy oid
cells
hype pola ize
on
lowe ing
ex e nal
Ca"
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
28
6)

THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
-
VOLUME
82
-
1983
(B uce
and
Ande son,
1979),
bu
cul u ed
goa
pa a hy oid
cells
a e
said
o
do
he
opposi e,
ha ing
a
es ing
po en ial
o
-29
.2
mV
in
0
.8
mM
Ca"
and
-44
.7
mV
in
2
.4
mM
Ca
+
(Sand
e
al
.,
1981)
.
Ou
measu e-
men s
on
a
pa a hy oid ag ee
quali a i ely
wi h
obse a ions
in
he
mouse,
bu
he
magni ude
o
ou
es ing
po en ials
is
-1
.5
imes
la ge
han
epo ed
o
mouse,
and
wice
as
la ge
as
he
epo ed
alues
o
cul u ed
goa
cells
.
The e
ha e
been
no
epo s
o spon aneous
spike
ac i i y,
ega dless
o
Ca"
concen a ion,
and
we
ha e
ound
none, e en
hough ou
cells
had
es ing
po en ials
o
e y
heal hy
magni ude
.
In
cul u ed
cells,
e-
gene a i e
esponses
a e
said
o
be
igge ed
by
injec ion
o
depola izing
cu en
h ough
he
mic oelec ode
(Sand
e
al
.,
1981)
.
The
high
elec-
ode
esis ance
and
low
inpu
esis ance
o he
gland
p e en ed
us
om
s imula ing
e ec i ely
h ough
he
mic oelec ode
.
Pa a hy oid
cells
in
he
a
a e
^,
8
,um
in
diame e
(Ro h
and
Raisz,
1964)
.
Using
1,000
SZ
cm'
as
a
guess
o
memb ane
esis ance
(Cole,
1968),
he
inpu
esis ance
would
be
498
MR
we e
he
cells
no coupled
o
each
o he by
junc ions
o lowe
esis ance
.
Fo
goa
pa a hy oid
cells
in
cul u e,
he
epo ed
igu e
is
503
±
218
MR
in
2
.4
mM
Ca"
and 290
±
198
MR
a
0
.8
mM
Ca"
.
We
epo
a
much
lowe
alue
o
inpu
esis ance
o
cells
in
he
gland,
24
.3
±
14
MO
.
This
s ongly sugges s
ha
in
he
pa a hy oid,
as in
o he
glands
(Pe e sen, 1980),
cells
a e
in e connec ed
by
low- esis ance
junc ions
.
F eeze- ac u e
eplicas
o
a
pa a hy oid
cells
ha e
con i med
he
exis ence
o
nume ous
gap
junc ions
(Ra azzola
and
O ci,
1977
;
Lopez-Ba neo
and
F anzini-A ms ong,
1982)
.
Possible
O igins
o
he
Depola iza ion
Induced
by
Di alen
Ca ions
I
is
i s
necessa y
o
conside
possible
bu
unin e es ing
explana ions
o
he
sensi i i y
o
memb ane
po en ial
o
Ca"
concen a ion
.
The
la ge
magni ude
o
he
es ing
po en ial
in
low
Ca"
makes
i
unlikely ha
we
ha e
p oblems
wi h
he
seal
be ween
memb ane
and
mic oelec ode
.
Fu he , he
inpu
esis ance
is
highe
in
2
.5
mM
Ca", when
he
cell
is
depola ized
.
The
depola iza ion
is
hus
unlikely
o
esul
om
a
ailu e
o
he
memb ane-elec ode
seal
.
A
second
possibili y
is
ha
aising
Ca"
causes
su icien
Ca"
en y
o
educe
coupling
be ween
cells
(De
Mello,
1975
;
Iwa suki
and
Pe e sen,
1977
;
Rose
and
Loewens ein,
1975)
.
This
could
lead
o
depola iza ion
o
he
impaled
cell
by
he
shun
esis ance
a ound
he
elec ode,
when
he
impaled
cell
is
no
longe
suppo ed by
i s
neighbo s
.
This
possibili y
can be
disca ded
on
he
g ounds
ha
Mg",
which
is
no mally
p esen
in
he
cell a
high
concen a ion
and
does no
cause
uncoupling
(De
Mello,
1975
;
Iwa suki
and
Pe e sen,
1977),
has
an
e ec
on
memb ane
po en ial
simila
o
Ca"
.
T ansi ion
elemen s
also
depola ize
pa a hy oid
cells,
al hough
hey
a e
e y
impe mean
and
do
no
di ec ly a ec
cell
coupling
.
On
occasion,
hey
e en
compe e
wi h
Ca"
and
es o e
cell
coupling
(Pe e sen,
1980)
.
Thy oid
ollicula
cells
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
LOPEz-BARNEO
AND
ARMSTRONG

Depola izing
Response
o
Ra
Pa a hy oid
Cells

287
om
he
a
a e
coupled
and
ha e
an
inpu
esis ance
alue
o
11
M12
(G een
and
Pe e sen,
1981)
.
Bo h
in
he
mouse
(B uce
and
Ande son,
1979)
and
in
he
a
(p esen
expe imen s),
he
es ing
po en ial
o
hy oid
cells
was
no
a ec ed
by changes
in
ex e nal
Ca"
in
he
ange
o
in e es
.
Thus,
bo h o
hese
unin e es ing
explana ions
a e
unlikely
.
The
po en ial
changes obse ed
a e
much
oo
la ge
o
be
accoun ed
o
as
a
di ec esul
o
a
change
in
he
equilib ium
po en ial
o
Ca"
.
E en
i
he
memb ane
we e
exclusi ely
Ca
+
pe meable,
changing
Ca"
om
1
.5
o
2
.5
mM
would
change
he
memb ane
po en ial
by
only
6
.7
mV,
much
less
han
he
obse ed
change
.
No
does
i
seem
likely
ha
Ca"
channels
o
he
ype
epo ed
in
o he
issues
play
a
pa
in
he
esponse
.
The
selec i i y
o
he
Ca"
channel
o
alkali-ea h
di alen
ca ions
(Hagiwa a
e
al
.,
1974
;
Hagiwa a,
1975)
con as s
wi h
ou
ind-
ings
in
pa a hy oid
cells,
whe e
no
quali a i e dis inc ion
be ween
he
ou
ca ions
(Ca",
S ",
Mg
++
,
and
Ba
++
)
was
seen
.
Ba
++
is
no
e y
e ec i e
in
depola izing
pa a hy oid
cells
al hough
i
pe mea es
well
h ough
he
Ca
channel
(Hagiwa a
e
al
.,
1974
;
Reu e ,
1973)
.
In
addi-
ion,
Co',
Cd
++
,
and
Mn
++
,
which
a e
Ca
++
channel
blocke s
(Bake
e
al
.,
1973
;
Kohlha d
e al
.,
1973
;
Hagiwa a,
1975),
mimic
he
e ec s
o
Ca++
a he
han blocking
he
esponse
.
Finally,
he
Ca++
channel
blocke
D600
(Kohlha d
e
al
.,
1972)
is
wi hou
e ec
on
he
esponse
o
aising
Thus,
i
seems
ha
pa a hy oid
cells
possess
an
unusual
calcium-sensing
mechanism
o
ex ao dina y
sensi i i y,
no obse ed
in
o he
biological
p epa a ions
.
A
simila
bu
much
smalle
esponse
is
seen
in
he
es ing
sec e o y
memb ane
o
eshwa e
lamellib anch
man les
.
A
10- old
de-
c ease
in
ex e nal
calcium
( om 6
o
0
.6
mM)
hype pola izes
by
6
mV
(So enson
e
al
.,
1980)
.
The
o de
o
e ec i eness
o
di alen
ca ions
in
depola izing
pa a hy-
oid
cells
is
e y
simila
o
he
a ini y
o
Ca-binding
p o eins
and
cal-
modulin-like
ecep o s
o
se e al
di alen
ca ions
.
I
is
known
ha
Mn++,
S ++,
Mg
++
,
and
Ba++ can bind
o
a
b ain
Ca
++
egula o y
p o ein
(Wol
e
al
.,
1977)
.
In
molluscan
neu ons,
ac i a ion
o
po assium
pe meabili y
by
in e nal
Ca++
(an
e ec
p obably
media ed
by a
Ca++
ecep o
loca ed
in
he
inne
side
o
he
memb ane)
is
simula ed
by
o he
di alen
ca ions
(Meech,
1974
;
Meech
and
S anden,
1975)
.
Ca
++
is
he
mos
e ec i e
ion,
ollowed
by Cd++,
S ++,
and
Mn++
.
The
ca ions
Ba++,
Co++,
M
g
++,
and
Zn
++
ha e
been
ound
o
be
e y
ine ec i e
(Go man
and
He mann,
1979)
.
Abou
he
same
o de
has
been
ound
in
he
exchange
o
a ious
di alen
ca ions
o
oponin-bound
"Ca
++
(Fuchs,
1971)
.
These
indings
sugges
ha
he
in e ac ion
o
di alen
ca ions
wi h
pa a hy oid
cells
is
no based
on
hei
di e en
pe meabili y
h ough
he
memb ane and
poin
owa d
he
possible
exis ence
o a
di alen
ca ion
ecep o
in
he
ex e nal
su ace
o
hese
cells
.
This
ecep o
could be a
Ca-binding
p o ein
wi h
a
di e en
a ini y
o
each
o
he
di alen
ca ions
ha
a ec
memb ane
ol age
.
Modi ica ions
in
memb ane
pe meabili y
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
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28
8

THE
JOURNAL
OF GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
by
con o ma ional
changes o
he
ecep o
a e
i
binds
o
one
o
se e al
di alen
ca ions
would
esul in
he
elec ical
e en s
associa ed
wi h
al e a ions
in
he
ex e nal
concen a ion
o
di alen
ca ions
.
Recen
mo phological
s udies
on
a
pa a hy oid
glands
using
he
eeze- ac u e
echnique
(Lopez-Ba neo
and
F anzini-A ms ong,
1982
;
C
.
F anzini-
A ms ong,
unpublished
obse a ions)
ha e
e ealed
he
exis ence
in
he
cell
memb ane
o
pa icles
ha
a e
densely
packed,
egula ly
dis ibu ed
h oughou
he
plasmalemma,
and
unusually
uni o m
in
size
.
One
migh
specula e
ha
hese
unusual
pa icles
a e
ecep o s,
whose
dense
packing
con e s
on
hese
cells
hei
ex ao dina y
Ca'
sensi i i y
.
Inpu
Resis ance
and
Memb ane
Resis ance
The
inpu
esis ance
(R
;)
in a
issue
ha
is
elec ically
in e connec ed
by
gap
junc ions
depends
on
bo h
junc ional
(R
j
)
and
memb ane
esis ance
(R
m)
.
The
change
ha
we
obse e
on
aising
ex e nal
Ca"
could
a ise
om
al e ing
ei he ac o
.
We
know
no
mechanism
by
which
ex acel-
lula
Mg"
o
ansi ion
elemen s
could
aise
junc ional
esis ance,
and
he e o e
we
suspec
ha
di alen
ca ions
al e
memb ane
esis ance
.
The
magni ude
o
he
R
mchange
signaled
by
a 2
.4- old
inc ease
in
R
;
depends
on
he
a io
R
;/Rm
(c
.
Holman
and
Neild,
1979,
o
a
somewha
di e en
conclusion)
.
To
app oach
his
p oblem
we
used
a
simple
model
o
he
issue,
which
was
adequa e
o
ou
pu poses
.
The
model
(Fig
.
11
A)
assumes
ha
he
pene a ed
cell
(1)
is
a
sphe e
o
adius
4
Am,
su ounded
by
sphe ical
shells
o
8
Am
hickness
.
The
shells
con ain
successi e
gen-
e a ions
o neighbo s
.
Fig
.
11B
illus a es
he
elec ical
ci cui
ha
co -
esponds
o
his
h ee-dimensional
a ay
assuming
ha
(a)
R
m
( esis ance
o
he
impaled
cell)
and
R
j
( esis ance
o
i s
junc ions
o
all
o
i s
nea es
neighbo s)
a e
he
same
o
all
cells,
and
(b)
he
esis i i y
o
ex acellula
and
in acellula
media
is
negligible
(Benne ,
1966
;
Socola
and
Loew-
ens ein,
1979)
.
To
acili a e
compu a ions,
only
h ee
shells
o
cells
(in
addi ion o
he
impaled
one)
ha e
been
conside ed
.
The
alues
o
Rm1,2,and9
and
RJiandI
(see
Fig
.
11
B) used
a e
gi en
in
he
igu e
legend
.
Sol ing
his
equi alen
ci cui yields
he
plo
shown
in
Fig
.
11
C
.
The
o dina e ep esen s
he
a io
R
;/R
.,
a
di e en alues
o
Rj/Rm,
as
gi en
on
he
abscissa
in
a
semilog
scale
.
The
cu e
shows
ha
when
R
;/Rm
is
la ge,
R
;/R
..
app oaches
uni y,
since
he
impaled
cell
is
well
isola ed
om
i s
neighbo s
and
inpu
esis ance
e lec s
only
he
memb ane
esis ance
o
he
impaled
cell
.
When
Rj/Rm
is
e y
small,
R
;/Rm
again
app oaches
uni y
because
he
eco ding
is
being
made
om
wha
is
in
essence
a
la ge
single
cell
.
Fo
in e media e
alues
o Rj/Rm,
i
can
be
seen
ha
R
;/RI,
is
much
smalle
han
uni y
and
he e o e
a
gi en
inc ease
in
Rn,
is
signaled
by
a
smalle
change
in
R
;
.
The
same
quali a i e
ela ionship
be ween
R
m
,
R
j
,
and
R
;
is
ob ained
wi h
a
wo-dimensional
model,
bu
he
minimal
R
;/
R
m
occu s
a
a
di e en
a io
o junc ional o
memb ane
esis ance
.
Pe meabili y
Changes
In ol ed
in
he
Response
o
High
Calcium
In
he
absence o o he
in o ma ion,
he
ol age
change induced
by
high
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
Published Augus 1, 1983
LOPEz-BARNEO
AND
ARMSTRONG
Depola izing
Response
o
Ra
Pa a hy oid
Cells

289
Ca"
could be
due
o
ei he
an
inc ease
o a
depola izing
conduc ance
o
a
dec ease
in
a
pola izing
conduc ance,
e
.g
.,
P
K
.
Neglec ing
he
con i-
bu ion
o
anions,
i
can
be
calcula ed
by
he
Goldman
(1943)
equa ion
ARiARm
A
B
Rm
Rj/Rm
5

1
0
.5
0
.1

0
.01

OA01

0
.0001
FIGURE
11
.
Cell- o-cell
coupling
in
he
pa a hy oid gland
.
A
shows
a
model
o
cell
opology
in
he
pa a hy oid
gland
.
The
impaled
cell
(I)
is
su ounded
by
sphe ical
shells
o
closely
packed
cells
.
The
i s ,
second,
and
hi d
shells
con ain
25,
97,
and
216
cells
.
B
shows
he
equi alen
elec ical
ci cui
o
his
model
.
R
m
is
he
memb ane
esis ance
o
a
single
cell,
and
R
j
is
he
pa allel
esis ance
o
he
junc ions
o
all
o
i s
neighbo s
.
Rm

RM
2
1
and
Rms
a e he
pa allel
memb ane
esis ance
o
he
i s ,
second,
and
hi d
shell
su ounding
he pene a ed
cell
and
a e,
espec i ely,
Rm/
25,
R
m
/97,
and
R
m
/216
.
R
j
,
and
RA
Y
a e
he
esul an
junc ional
esis ance
be ween
he
i s
and
he
second
shells
and
be ween
he
second
and
he
hi d
shells
.
These
alues
a e
25R
j
/97 and
25R
;/216,
espec i ely
.
C
illus a es
ha
he
a io
o
he
change
in
inpu
esis ance
o
he
change
in
memb ane
esis ance
(R
;/R
.)
depends
on
he
a io
Rj/Rm
(abscissa)
.
The
in e up ed
line
is
d awn
a
a
a io
R
;/R,,,
o
0
.3
(a
gi en
change
in
R
m
esul s
in
a
change
in
R
;
ha
is
smalle
by
a
ac o
o
0
.33)
.
ha
i
a
depola iza ion
o 39
mV
(-73
mV
a
1
.5
Ca"
and
-34
mV
a
2
.5
mM
Ca")
we e
due
o
a
dec ease
in
P
K
,
a 7
.9- old
inc ease
in
memb ane
pe meabili y
would
be obse ed
ha
would
be
e lec ed
in
an
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
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29
0
THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
R

,
change
o abou
he
same
size
.
This
calcula ion
is
done
assuming
10
mM
as
he
in acellula
concen a ion
o
Na
and 160
mM
(es ima ed
om
he
plo
in
Fig
.
10)
as
he
in acellula
concen a ion
o
K
+
.
In
a
coupled
issue,
an
8- old
inc ease
in
R
m
can
esul
in
a2
.4- old
R
;
change,
only
30%
as
la ge
as
he
R
m
change,
as
discussed
abo e
.
The
in e up ed
line in
Fig
.
I
1
C
shows
ha
wi h
he
h ee-dimensional
model,
wo
di e en
Rj/Rm
a ios
could
gi e
an
R
;/R
m
a io
o
his
alue
.
R
;/R
m
nea
0
.01
seems
a
easonable
a io
o
a
well-coupled
issue
.
The e o e,
i is
no
impossible
ha
he
depola iza ion seen
in
high
Ca"
is
due
o a
supp ession
o
K+
pe meabili y
.
Cla i ica ion
o
his
poin
mus
awai
mo e
explici
da a
on
Rm,
and
his
will
necessa ily
in ol e
elec ically
isola ed
cells
.
Rela ionship
Be ween
Memb ane
Elec ical
E en s
and
PTH
Sec e ion
In
he
mouse
(B uce
and
Ande son,
1979)
and
in
he
a
(p esen
expe imen s),
he
ela ionship
be ween
memb ane
po en ial
and
ex e nal
Ca"
is
e y
simila
o
he
ela ionship
be ween
PTH
elease
and
ex e nal
Ca"
obse ed
in
he
cow,
bo h
in
i o
(Maye
and
Hu s ,
1978)
and
in
i o
(B own
e
al
.,
1976
;
Habene and
Po s,
1976)
.
PTH
elease
and
memb ane
po en ial
as
a
unc ion
o ex e nal
Ca"
a e
illus a ed in
Fig
.
12
.
Pa
A
has
been
ed awn
om
Habene
and
Po s
(1976)
and
pa
B
is
based
on
ou
expe imen al
da a
.
Bo h
cu es
a e
e y
s eep
and
compa able,
al hough
he e
is
a
shi
o
0
.2-0
.3
mM
along
he
Ca"
concen a ion
axis
when
hey
a e
supe imposed
.
This
shi
may
be
ela ed
o
di e ences
be ween
animal
species
o
o
di e ences
in
calcium
ac i i y
be ween
solu ions
used
in
biochemical
and
elec ophysiological
expe i-
men s
.
We
a e no
awa e
o
he
exis ence
o
in o ma ion
ela ing
PTH
elease
and
ex e nal
Ca"
in
he
a
.
Howe e ,
he
Ca"
ange
in
which
a
s eep
change
in
memb ane
ol age
is
seen (1-2
.5
mM)
is
e y
simila
o
he
ange o e
which
e e sible
mo phological
changes
a e
seen
in
cul u ed
a
pa a hy oid
glands
(1
.3-2
.7
mM
;
Ro h
and
Raisz,
1964)
.
O he
di alen
ca ions
also
ha e
pa allel e ec s
on
memb ane
ol age
and
PTH
sec e ion
.
Mg"
is
2
.5
imes
less
e icien
han
Ca"
in
dec easing
PTH
sec e ion
(Habene
and
Po s,
1976
;
She wood
e
al
.,
1970),
and
we
ind ha
i is
^-2
.4
imes
less
po en
han
Ca"
in
depola izing
pa a hy oid
cells
.
I
has
ecen ly
been
obse ed
ha
Mn"
and
S "
a e
e y
e ec i e
in
inhibi ing
PTH
sec e ion
and
ha
Ba
++
is
a
poo
Ca"
subs i u e
in
dec easing
PTH
elease
(Wallace
and
Sca pa,
1982)
.
This
co esponds
qui e
well
wi h
hei
depola izing
po ency
in
ou
expe i-
men s
.
O he
poin s
o
pa allelism
be ween
memb ane
ol age
and
sec e ion
a e
ha
ouabain
inhibi s
PTH
sec e ion,
possibly
by
depola izing
he
cells
(B own
e
al
.,
1981
;
Fische
e
al
.,
1982),
and
ha
comple e
emo al
o
ex e nal
Na'
(which
we
ha e
shown
does
no
subs an ially
a ec
he
memb ane
po en ial)
does
no
al e
he
modula ion by
ex e nal
Ca"
o
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
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LOPEz-BARNEO
AND
ARMSTRONG

Depola izing
Response
o
Ra
Pa a hy oid
Cells

291
PTH
sec e ion
in
dispe sed
cells
om
he
cow
(Fische
e
al
.,
1982
;
Wallace
and
Sca pa,
1982)
.
Taken
oge he ,
hese
da a
s ongly
sugges
ha
in
pa a hy oid
cells,
hype pola iza ion
is
associa ed
wi h
inc eased
sec e ion,
and
depola iza ion
wi h
dec eased
sec e ion
.
A
sepa a e
mechanism,
media ed
by
CAMP,
may
also exis
.
Isop o e -
enol
is
a
po en
sec e agogue
o
PTH
elease
(B own
e
al
.,
1977
;
Fische
e
al
.,
1982),
al hough
i
does no
seem
o
modi y
memb ane
po en ial
.
Isop o e enol
ac i a ion
o
PTH
elease, in
con as
o
low-Ca"-ac i a ed
sec e ion
(Fische
e al
.,
1982),
is
accompanied
by a
la ge inc ease
in
A
PTH
elease

memb ane
N

po en ial
(mV)
B
-70~
-60-
-40~
-30-
0
.5

1

1
.5

2

2
.S[Ca++I

0
.5

1

5

2

i5
1C0++1
MM

MM
FIGURE
12
.

Ca'
al e a ions
a ec
PTH
sec e ion
and
memb ane
po en-
ial
in
pa allel
.
A
has
been
ed awn om
he
da a
o
Habene and
Po s
(1976)
on
slices
o
cal
pa a hy oid
glands
main ained
in
i o
.
The
pe cen
o
immuno eac i e
PTH
is
gi en
in
he
o dina e
and
Ca
++
concen a ion
in
he
abscissa
.
The
Mg++
concen a ion
was
held
cons an
a
0
.8
mM
.
Poin s
ep esen
he
means
o
ou
o
six
measu emen s
.
B
is
om
ou
esul s
on
he
a
.
The
Mg
++
concen a ion
was
held
cons an
a
1
.1
mM
.
Poin s
ep esen
he
means
o
3-66
measu emen s
.
in acellula
cAMP
(B own
e
al
.,
1977
;
Fische
e
al
.,
1982)
.
This co espondence
be ween
memb ane
ol age
and
sec e ion
con-
as s
wi h
he
usual
sequence o
e en s
ound
in
o he
glands,
whe e
he
physiological
s imulan s
o
sec e ion
e oke
a
memb ane
depola iza ion
ha
opens
ol age-dependen
Ca"
channels
.
Ca"
en y
h ough
hese
channels
seems
o
be
esponsible
o
igge ing
exocy osis,
and
emo al
o
di alen
ca ions
om
he
ex e nal
solu ion
u ns
o
sec e ion
(Pe e sen,
1980
;
Rubin, 1970)
.
The e
seem
o
be
some
excep ions
o
his
usual
pa e n
.
Fo
example,
jux aglome ula
cells
hype pola ize
by 8-10
mV
on Sep embe 22, 2014jgp. up ess.o gDownloaded om
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29
2

THE
JOURNAL
OF
GENERAL
PHYSIOLOGY
"
VOLUME
82
-
1983
a e
addi ion o
ad enaline,
which
is
a
s imulan
o
enin
sec e ion
(Fishman,
1976)
.
In
hese
cells,
comple e
emo al
o ex e nal
Ca"
and
inc ease
o
Mg"
s imula e
enin
elease
(F ay,
1977)
.
In addi ion o
he
elec ophysiological indings
and
he
e ec
o
di alen
ca ions
on
PTH
sec e ion,
o he
e idence
suppo s he
iew
ha
he
mechanism
o
s imulus sec e ion-coupling
in
he
pa a hy oid
gland
is
somehow
unusual
.
Fully
e e sible
sec e o y
ac i i y
can be obse ed
in
dispe sed
cells
in
he
absence o
Ca"
.
Fu he ,
la ge
doses
(up
o 10
-4
M)
o
he
Ca"
channel
blocke
D600
ha e
no
e ec
on
PTH
sec e ion
ac i a ed
by low
Ca"
(Wallace
e
al
.,
1983)
.
Finally,
i
is
known
ha
he
di alen
ca ion
ionopho e
A23187,
which
p esumably
inc eases
cy osolic
Ca"
(Reed
and
La dy,
1972),
inhibi s
PTH
sec e ion
(B own
e
al
.,
1980
;
Fische
e
al
.,
1982
;
Habene
e al
.,
1977)
.
In
summa y,
memb ane
po en ial
o
pa a hy oid
cells
is
s eeply
de-
penden
on
ex e nal
Ca"
in
he
physiological
ange
.
I
seems
highly
likely
ha
he
memb ane
po en ial
change
is
ela ed
o
a
change
in
sec e o y
ac i i y
(Fig
.
12)
.
The
ela ion
be ween
memb ane
ol age,
calcium,
and
sec e ion
is
e y
unusual
and
sugges s
he
exis ence
o a
s imulus-sec e ion
coupling
mechanism
ha
has
no
p eceden
in
he
li e a u e
.
The
mecha-
nism o
his
coupling
and
he
pe meabili ies
in ol ed
in
he
Ca"-induced
depola iza ion
emain
o
be
sol ed
.
We
a e g a e ul o
Lin-E Lin
o
he
con ibu ions
o
some
o
he
expe imen s
.
Suppo ed
by
Na ional
Ins i u es
o Heal h
g an
NS
12547,
and
by
an
NIH
In e na ional
Pos doc o al
Fellowship
o
J
.
Lopez-Ba neo
.
Recei ed
o
publica ion
9
Augus
1982
and
in
e ised
o m
29
Ap il
1983
.
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