Download Membrane of Striated Muscle

Movement of Inorganic Ions across the
Membrane of Striated Muscle
By R. H. ADRIAN, M.D., B.Chir.
The unidirectional fluxes of sodium, chloride, anid potassium across the mnembrane of striated
muscle cells are described under a number of experiniental conditions. The results are compared with the predicted behavior of simple membranes. With the possible exception of
chloride, it is concluded that the movements of these ions cannot be described without postulating variable permeabilities or a variable nunmber of 'carriers' or 'sites' in the membrane.
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IT IS NOW widely accepted that many substances cross cellular membranes by special
mechanisms. The movement of an ion into a
region of greater electrochemical potential
plainly requires a mechanism which can be
linked to a source of energy, but even movements down gradients of chemical or electrochemical potential may require special mechanisms if they are to take place with sufficient
speed. The facilitated diffusion of glucose
across the wall of the red cell is an example.
It is becoming increasingly clear that the
movements of many inorganic ions across the
surface membrane of muscle cells cannot be
explained in terms of diffusional and electrical forces only.
A muscle cell is thought to maintain its
internal ionic composition by pumping out
the sodium that enters the cell by diffusion down the sodium coneentration gradient.
Linked to the driven outward sodium movement, but not necessarily in a 1 to 1
manner, there is an inward potassium movement. The potential across the cell membrane
will have a value such that the potassium
lost from the cell by movement down its concentration gradient is balanced by the active
uptake. Since the electrochemical potential
of chloride appears to be equal on either side
of the membrane, there is no need to postulate
any energy-consuming mechanism influencing
chloride movements. This description is probably valid as a general outline of the situa-
tion,' though there is disagreement on the
occurrence of linked sodium and potassium
movements.2'3 A number of authors do not
agree that a sodium pump is necessary and
prefer to consider that the high, internal potassium concentration of nerve and muscle
cells is the result of binding on selective sites
distributed throughout the substance of the
cell.4' 6 In what follows I will assume that the
internal ions behave as if they were in free
solution and that the rate-limiting step for
ionic movements resides within the plasma
membrane. But even making this assumption
we are faced with a large number of unanswered questions about how ions move in
the membrane.
For an ion which is- acted on only by the
forces of thermal agitation and electrical potenitial, and which does not compete for chemical combination with a molecule in the membrane, the ratio of the outward flux (M0llt)
to the inward flux (Min) is given by
Mout _ C ep (zEF
where E is the internal potential, z the algebraic valency, and Cin and C0,,t the internal
and external concentration. The activity coefficients on the inside and outside are assumed to be equal. This equation was first
derived by Behn (1897) and has been discussed by Ussing, Teorell, and Hodgkin among
others.6-9 The equation is independent of
variations within the membrane of potential,
concentration, activity coefficient, and mobility. It does not, however, tell us the magni-
From the Physiology Laboratory, Cambridge University, Cambridge, England.
1214
Circulation, Volume XXVI, November 1965
SYMPOSIUM ON THE PLASMA MEMBRANE
tude of either flux. To calculate the individual
fluxes and the way in which they vary with
membrane potential and concentration, one
has to make assumptions about the way in
which the potential, activity, and mobility
vary within the membrane.
The assumptions which lead to the most
manageable flux equations are that the mobilitv of the ion is constant across the membrane and that the potential in the membrane
varies linearly. This is generally called the
constant-field assumption and was first made
by Goldman.10 The equations for the two
fluxes of a monovalent cation are
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(E4)
(
EF Cin exp EF
( RT)
(2)
Mout
RT exp
-1
Gout (Zr) - (1(3)
Mn= P EF
RT,exp
where P is a permeability eonstant of the
and has the dimensions of
form aF
cm./see." The thickness of the membrane is
a; u is the mobility in the membrane, and /
is the partition coefficient for the ion between
the membrane and the aqueous solution. The
assumption of a constant field has been widely
used and as widely criticized. Other equations
for the fluxes have been based on other assumptions about the potential, concentration
gradient, and activity within the membrane.
Teorell has shown that in membranes with
fixed charges the potential gradient is not
linear, and he has derived flux equations for
fixed charge membranes.12 Linderholm13 has
treated the case of a membrane with no fixed
charges in which the activity coefficient varies
with the concentration. But these equations
have in common with the constant-field equations the fact that the flux ratio obeys equation 1. They all predict that so long as the
membrane potential remains unchanged and
the total concentrations on each side of the
membrane are the same, then the effiux of a
ulRT
Circulation, Volume XXVI, November 1962
1215
particular ion will depend on the internal
concentration of that ion, the influx of the
same ion will depend on its external concentration, and both fluxes will be directly proportional to the mobility of the ion in the
membrane. This fundamental similarity of
the flux equations arises because they are all
based on the assumption that the chance of
any one ion crossing the membrane is uninfluenced by the presence of any other ion inside or outside; in other words that the ions
cross the membrane independently of each
other.
The flux ratio equation has only been tested
over a wide range of potential and external
concentration in the case of giant axons from
the cuttlefish Sepia. Hodgkin and Keynes'4
measured the two fluxes in axons poisoned
with DNP to eliminate pumped-inward potassium movement. They found that the logarithm of the flux ratio varied more steeply
with potential than was predicted by equation
1 for a monovalent cation. They explained
their results by supposing that potassium
crossed the membrane along a chain of negatively charged sites or through long narrow
pores. The essential feature of both explanations is that in any one chain of sites or in
alny one tube, ions move in single file and can
not pass one another.
Ussing15 has suggested a mechanism whieh
will account for deviations from the flux ratio
equation in the opposite direction-for a flux
ratio which is less sensitive to changes in
potential and concentration than predicted
by equation 1. If a carrier molecule exists
in the membrane which is unable to cross
from one side to the other unless combined
with a particular kind of ion, there will be
equal and opposite movements of this ion
carried across the membrane by the movement
of the ion-carrier complex. If the carrier is
unable to combine with any other ion and
unable to cross the membrane uncombined,
the magnitude of the equal carrier-born influx and effliux will be independent of the
membrane potential and dependent on the
concentrations on either side of the membrane. Since the influx must always equal
ADRIAN
1216
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fiber at rest (iuiside -92 mV) is so
far removed fromn the sodium equilibrium
potential (inside +50 mV) fluxes of sodium
resultiing froim thermal alnd electrical forces
alonie would be verv unequal. The efflux would
onlv be 0.003 of the influx. ,Experimentally
the iinflux anid efflux are about equal for a
musele in Ringer Is fluid and both are about
10 pmiiole cm.2/see. If half the sodium efflux
is by an exchange diffusion mechanism, half
the sodiumii influx is by the same nmechanism,
and 3 pmole/ccm.2 see. represents the passive
influx which imlust be balaneed by the pump.
Applying the constant-field equatioin for the
influx (equation 3), a flux of 5 pmole/em.2/
see. corresponds to a PNa of 0.01 X 10-6Cm./
see., which is in satisfactory agreement with
estimates of P,- by electrical methods. 7
Keylnes amnd Swan have also shown that in
eircumstaniees where the intermnal sodium
mLuscle
the efflux there can be no net movement of
an ion by such a mechanism.
Keynes and Swan'6 have showin that the
efflux of 24Na from a sartorius muscle into
an ordinary frog Ringer's solution is reduced
byimore thami 50 per eeiit wheni the sodium in
the Ringer's fluid is replaced bv lithiuni or
choline. They also founid that the removal of
extracellular potassiuni reduced the efflux of
24Na. Removal of both sodium and potassium
produced a larger reductioni of efflux thain
the renioval of either alone. Thev studied the
concenL
relatiomi between the external sodium
could
which
of
efflux
the
sodium,
tration and
of
equation
an
by
be reasonably well fitted
the Michaelis-Menten type with a half-saturation value for the externial sodiumn concentratiomi of 38 mM (fig. 1, from Keynes and Swan,
1959).
Because the membrane potential of the
100
-
90_
.
x
80
0
x
-,
0
x
4)
-
0
c
70
0-o
60
4-
50
40
0
100
80
60
40
20
External Na concentration (mM)
Figure 1
The relative magnitude of the efflux of 24Na. when the external sodium is varied by
substituting lithium. (From Keynes and Swann, 1959.16)
SYMPOSIUM ON THE PLASMA MEMBRANE
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might be expected to have risen, the exchange
diffusion component of the sodium efflux diminishes and the potassium coupled component increases. They make the attractive
suggestion that the Na-Na exchange carrier
can be changed into a carrier, which, when
coupled to a source of energy, moves sodium
out and potassium in. The proportion of the
carrier existing in either form might depend
on the internal sodium concentration. Such a
mechanism would tend to keep the internal
sodium concentration at a fixed level. In these
terms exchange diffusion of sodium can be
thought of as what the sodium pump does
when it is not required to move sodium and
potassium up their electrochemical gradients.
It is not surprising that special mechanisms
are needed to explain the movements of sodium, because muscle cells, and indeed most
cells, exist in a steady state with the electrochemical potential of sodium inside and outside far from equal. In frog muscle the distribution of the chloride ion seems to be what
would be expected if chloride were acted on
by thermal and electrical forces only.'8 Provided sufficient time is given to reach equilibrium, the ratio of the internal and external
concentrations of chloride is given by the
equation
/EF1
Ciln
Clt = exp kRT)
but even so it is not yet clear whether the
movements of chloride in each direction are
independent. Hodgkin and Horowicz17 and
Adrian's have both suggested that chloride
may cross the muscle membrane by single-file
mechanism of the kind postulated for the passive potassium fluxes of Sepia. From experiments on isolated muscle -fibers from the
semitendinosus of the frog, Hodgkin and
Horowiez concluded that the net movement of
chloride under a wide variety of conditions
could be predicted by the constant-field equation with a mean value for Pc1 of 4 X 10-6
cm./see. When the influx and efflux of chloride are equal, the constant-field equation
takes the form,
-CIO
Mi= = Mout = Pl
ClO - Cl1 ln Cl1
(4)
1217
Setting Pc1 = 4 x 10-6 cm/sec., this equation
predicts that a muscle in equilibrium with a
Ringer's solution which contains 50 mM/
l.-KCl and 120 m-mole/l.-NaCl will have a
chloride efflux of 330 pmole/cm.2/see. In equilibrium with a similar solution with 100 mmole/l.-KCl, the efflux would be 540 pmole/
Cm.2/sec. The effluxes under both conditions
have been measured'8' 19 and are found to be
respectively 50 and 200 pmole/Cm.2/see. The
number of observations is not large, but if
the discrepancy is a real one it is of the kind
that would be expected if there were a singlefile mechanism. Adrian and Freygang (in
press) have recently made conductance measurements on fibers in the sartorius musele.
In the 100 mM KCl solution referred to,
above they estimated Pci to be 2.2 X 10-6
cm./see., which would go some way to resolving the discrepancy, since the fluxes were
measured on sartorius muscle. Their experiments also suggest a fairly wide variation of
Pc1 from one muscle to another.
Replacement of the external chloride with
a number of anions, for instance NO3-, I-,
CNS-, C104-, reduces the chloride efflux.20'
In the case of nitrate, 100 per cent replacement of the external chloride halves the efflux
of 36C1. Figure 2 shows the reverse effect, that
the efflux of 36Cl increases when chloride replaces external nitrate. When nitrate replaces
chloride the membrane resistance rises sub-stantially, but there appears to be little or ncp
alteration in the membrane potential.'7 18,21
Two conclusions can be drawn; that chloride
in the presence of nitrate has about the same
permeability as nitrate; and that the component of the efflux which disappears when nitrate replaces chloride is not an exchange
diffusion flux. If half the chloride efflux were
an exchange diffusion flux, there should be no
alteration of membrane resistance when nitrate replaces chloride. It is reasonable to
conclude that the presence of nitrate alters
the permeability to chloride, that is, it alters
the ease with which chloride moves within
the membrane, or the concentration of chloride within the membrane, or both.
If the chloride movements are independent
1218
ADRIAN
but at the same tiine involve special carriers
or pores, these mechanisms cannot be near
saturation. For nitrate to affect the chloride
flux it would have to occupy a substantial
proportion of the carrier molecules or pores.
This would be possible if the affinity of the
carrier were much greater for nitrate than
for chloride, but since the perineabilities of
nitrate and chloride are comparable, the mobilitv of the nitrate-carrier complex would
1000-
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ftf
UX
from
of
CI
Sar tor ius
U
IO
E
N03
CI
of carrying a eurrent of potassium ions, but
they appear to rectify in opposite directions.
There certaiiily exists in muscle a mechanism
similar to the nerve mechanism and responsible for the rapid falling phase of the action
potential (delayed rectification). This mechanism has not been studied in detail in muscle,
because so far it has not proved possible to
apply voltage-clamp techniques to muscle fibers capable of conducting action potentials.
In high potassium most of the potassium
movement appears to be by a channel which
presents a high resistance when the net movement is in an outward direction (anomalous
rectification). Katz22 showed that when the
internal and external potassium concentration
were nmade equal and there was no other ion
which could carry current, the membrane
showed a remarkable asymmetry, having a
low resistance for inward current and a high
resistaniee for outward current. Figure 3
shows the same kind of current-voltage relation obtained from an isolated muscle fiber
in a sulfate solution with an external potassium coneentration of 100 mM.
WVhile the possibility exists that the passage
Im, Ja/cm2
*Ir
0.l
6.
20
40
60
80
100
*1-11*
4.
mi n utes
Figure 2
The rate of loss of 36C1 into NOs-Ringer's fluid
and subsequently into Cl-Ringer's fluid. (From
Adrian, 1961.18)
2.4
I
-30
-20
|
-10
|
b
a*
1.
10
.
,
,
,
20
30
40
50
J, 2.
*
have to be inuch less than the mobility of the
chloride-carrier complex. If the movements
of chloride are not independent, special assumptions are needed to explain the fact that
net movement appears to fit the constant-field
equation.17 At the moment there is insuffi,ient experimental evidence.
In muscle as opposed to nerve, there is
some evidence that there are two channels for
the movement of potassium into and out
of the fiber.28 Both channels are capable
|
IC
,~~~~~~~~---
60
Va, mV
4A
-I
6
8.
I0J
Figure 3
Current-voltage relation of an isolated fiber in
a S04-solution isotonic with Ringer's fluid and
containing 100 mMlI. K. Outwarcd membrane
current plotted in an upward direction. Abscissa
is thl alterationi of the membrane potential from
its resting value which was -10 mV. (From
Freyilgang and Adrian, 1961.28
1219
SYMPOSIUM ON THE PLASMA MEMBRANE
of anions can be explained by a fixed number
of specialized membrane sites, whether pores
or carriers, a similar mechanism with a fixed
number of sites is very much harder to visualize in the case of these passive potassium
movements. A system with a fixed quantity
of carrier or a fixed number of pores which
interact only with potassium could not show
the asymmetric current voltage relation of
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figure 3. Hypotheses involving multiplycharged carriers can be made to rectify in
this way but only if the total quantity of carrier is allowed to vary. Equally an equation
of the constant-field type with a constant permeability coefficient will not describe the behavior in figure 3, though, by appropriately
varying the permeability coefficient with potential, this or indeed any other current-voltage relation can be imitated. The validity or
usefulness of such arbitrary variation of the
permeability "constant" has given rise to a
good deal of discussion.23 24 25
The potassium current can be considered as
the difference between the influx and efflux
of potassium when these are altered by altering the membrane potential. It is therefore
of interest to study the two fluxes separately
under conditions of net potassium movement.
It is difficult to alter the membrane potential
of muscle by electrical methods during the
course of a tracer experiment, but one may
do so by making use of situations where the
chloride permeability is much greater than
the potassium permeability, and the membrane potential therefore controlled by the
chloride concentration ratio.17 Muscles were
loaded with extra internal potassium and
chloride by putting them into a Ringer's solution with a KCl concentration of 100 mM
and a NaCl concentration of 120 mM. They
reach a steady state in this solution in
about 3 hours with an extra 100 mM/l. of
both potassium and chloride internally. If
the internal potassium has been labeled with
42K, the steady state efflux into the high KCl
solution is found to be about 100 pmole/em.2/
sec. Figure 4 shows the effect on the membrane potential and the rate constant for the
loss of 42K of replacing the external chloride
Circulation, Volume XXVI, November 1962
with sulfate but leaving the external potassium concentration unaltered at 100 mM. The
solutions were arranged so that no immediate
movement of water takes place when they are
changed. The inside potential alters suddenly
from -20 mV to +50 mV. In this situation
there should be net outward movements of
both potassium and chloride, and they can be
shown to occur by direct chemical analysis.26
But the efflux of potassium drops. Since there
is a net outward movement the influx must
also have dropped. One may say then that
with constant concentrations on either side of
the membrane both efflux and influx are reduced when the potential is altered in a direction that would lead one to expect an
increased efflux, if the permeability were
constant.
If after a similar period in the high KCl
+60h
+40
E
2+20
a
c '4
, _--O~
c-20
2
3
Hours
Figure 4
The internal potential and the rate constant for
the loss of 42K measured on two similarly treated
muscles. At the beginning of each experiment., the
muscle had been in a solution containing 100
mM KCI and 119 mM NaCI. Sucrose aind SO4
were used to replace Cl isomotically. The external
K concentration remained unaltered throughout.
1220
ADRIAN
solution, a muscle is transferred to a solution
with the same chloride concentration but with
sodium, lithium, or choline replacing most
or all of the potassium, the potential remains
unaltered but the efflux of 42K drops by a
factor of 10 or more (fig. 5). Preliminary
E
-
I
~
2.5
->
100 mM
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.01
100 pmole/cm.2/sec.28 Harris and Sjodin24
have suggested that, in circumstances where
the influx and efflux of potassium are equal,
all transfer of isotope takes place by an exchange diffusion mechanism, with a fixed
number of potassium-saturated sites in an
outer region of the cell. A difficulty of such
a scheme is that the potassium conductance
must be zero when the membrane potential
equals the potassium equilibrium potential
and the influx and efflux are equal.
Sjodin27 suggested that rubidium and caesium alter the permeability of the muscle
membrane to potassium, and he has shown
recently25 that rubidium and caesium reduce
the uptake of 42K by muscle. To account for
these effects, he has suggested that rubidium,
caesium, and potassium compete for a fixed
number of sites in the membrane which are
not necessarily saturated. In the absence of
a competing ion, the uptake of each ion as a
function of its external concentration is supposed to be given by the equation
M1 (in)
.00
Hou rs
Figure 5
An experiment similar to the one shown in figure
4, but in this case the external CI concentration
was unaltered and the external K concentration
was reduced from 100 mM to 2.5 mM by the
substitution of Na.
experiments indicate that the influx drops by
than would be expected if it depended
only on the external potassium concentration.
The effect of removing external potassium on
the efflux of potassium is reminiscent of the
exchange diffusion of Na, but the mechanism
of the potassium effect cannot be the same
because, if only one tenth of the steady state
flux were capable of carrying current, the
potassium conductance of the membrane in
the high-KCl solution would be very small.
Conductance measurements in the high-KCl
solutions are consistent with a flux of about
-
PIN kiCikiCi(out)(olut)+ 1
(5)
N is the number of sites in the cell surface;
Pi and ki are a pair of constants which Sjodin
has compared to the mobility and partition
terms in the constant-field permeability coefficient. The values of Pi and ki for each of
the three ions are obtained by fitting the uptake rates of 42K, 86Rb, and 137Cs at various
external concentrations to the above equation.
When two competing ion species are present,
the uptake of one of them is supposed to be
given by the equation
more
(out)
PiN k'C' (otit) kiCi
+ kiCi (out) + 1 (6)
where k' and C'(0ut) are the appropriate con-
Mi (in)
stant and the external concentration of the
competing ion. He has achieved an impressive
agreement between the theoretical and experinental uptakes under a variety of conditions.
However, the agreement must be to some extent a coincidence since it is a feature of
Sjodin's model that the influxes are independent of the membrane potential, and we have
Circulation, Volume XXVI, November 1962
0.021-
'CLO 220 mM
\
Ko 100-1
2.5
1-50-1-100-1
10
1-25-1-100 mM
min I
0
0
0
0.01
U0
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0
0
2
1
3
4
hours
Figure 6
The rate constant for the loss of 42K from a KCl-loaded muscle into solutions with the
same Cl concentration but varying K concentrations. Na replaced K.
0.02
Clo-220 mM
nx nI
Ko 100-I
0
1-100---
-100 mM-
0
I-Rbo 100-1-50
0mM-I
0
0.0
c
0
tr
0
.I.
4
0
5
6
hours
Figure 7
The rate constant for the loss of 42K from a KC1-loaded muscle into solutions with
100 mMK or with no K and varying Rb concentration. The Cl concentration was the
same throughout the experiment. The total cation concentration was maintained with Na.
1221
ADRIAN
1222
seen that in some circumstances this is not so.
The effiux of an ion in Sjodin's model is, however, supposed to depend on the menibrane
potential as well as on the internal concentration, but the potential dependence predicted is in the opposite direction to that
found experimentally (fig. 4).
By an extension of the kind of experiment
shown in figure 5, one can determine the relation between the efflux of 42K and the external potassiuim concentration at substantially constant membrane potential. Figures
6 and 7 show two such experiments, and figure
8 shows the mean effluxes from a number of
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OCF
_
C-
B-~~~~
BO!,
E
° 60
<40
References
f
eJ
//
1
0
20
0
///
10
ment of potassium, but there is ani optim-iumn
rubidium concentration somewhere between
10 and 50 mM. Plainly rubidiunm does not
merely act as if it were sodium or lithium in
thlis situation; a conclusion which is reinforced
by the observation that the efflux of potassium
is very much reduced by the presence of rubidium, even though the muscle is in a situation where chloride, potassium, and rubidium
are in electrochemical equilibrium.
As far as potassium movements are concerned, the classical equations which relate
ionic movements to concentration and electrical force are inadequate, except ill a purely
formal way which turns the perineabilitv constant into an empirical variable. But equally
the existing carrier or pore hypotheses are
unable to cope with the experimental findings.
Better understanding of the mechanisms involved depends upon our ability to separate
experimnentally the effects of internal and external concentrations on both fluxes at constant potential fromn the effects on both fluxes
of potential at constant concentration.
20
30
100
50
Externol concentration
of
K or Rb
mM
Figure 8
Relative magnitude of the efflux of 4 2K into
solutions vith constant Cl concentration but with
varying K concentration (open circles) or with
varying Rb concentration (solid circles).
such experiments plotted against the external
concentration of either potassium or rubidium. The effluxes are expressed as a percentage
of the efflux into the high KCI solution with
which the contents of the fibers are in equilibrium.
It is something of a mystery that the ability
of potassium ions to carry current in an outward direction should depend on the external
potassium concentration. Rubidium in low
concentration promotes the outward move-
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activity in giant nerve fibres. Proe. Roy. Soc.
(London) B 148: 1, 1957.
2. CONWAY, E. J.: The nature and significance of
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84, 1957.
3. CONWAY, E. J.: Principles underlying the exchanges of K and Na ions across cell membranes. J. Gen. Physiol., suppl., 43: 17, 1960.
4. LINTG, G. N.: The interpretation of selective
ionic permeability and cellular potentials in
terms of the fixed charge-induction hypothesis.
J. Gen. Physiol., supp., 43: 149. 1960.
5. SHAW, F. H., SIMON, S. E., BENNET, S., AND
MULLER, M.: The relationship between sodium,
potassium and chloride in amphibian muscle.
J. Gen. Physiol. 40: 753, 1957.
6. BEHN, U.: Ueber wechselseitige Diffusion von
Electrolyten in verdfinnten wiisseringen Losungen unbesondere fiber Diffusion gegen das
Concentration-gefdlle. Ann. Phys. Chem. Neue
Folge 62: 54, 1897.
7. USSImNG, H. H.: In The Alkali Metals in Biology,
by H. H. Ussing, P. Kruhoffer, J. Hess
Thaysen, and N. A. Thorn. Berlin, SpringerVerlag, 1960.
Circulation, Volume XXVI, November 1962
SYMPOSIUM ON THE PLASMA MEMBRANE
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8. TEORELL, T.: Membrane electrophoresis in relation to bioelectrical polarization effects. Arch.
Sci. Physiol. 3: 205, 1949.
9. HODGxKIN, A. L.: The ionic basis of electrical
activity in nerve and muscle. Biol. Rev. 26:
339, 1951.
10. GOLDMAN, D. E.: Potential, impedance and
rectification in membranes. J. Gen. Physiol.
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11. HODGKIN, A. L., AND KATZ, B.: The effect of
sodium ions on the electrical activity of the
giant axon of the squid. J. Physiol. 108: 37,
1949.
12. TEORELL, T.: Transport processes and electrical
phenomena in ionic membranes. In Progress
in Biophysics, vol. 3. London, Pergamon Press,
1953.
13. LINDERUOLM, H.: Active transport of ions
through frog skin with special reference to
the action of certain diuretics. Acta Physiol.
Scand., suppl., 27: 97, 1952.
14. HODGKIN, A. L., AND KEYNES, R. D.: The potassium permeability of a giant nerve fibre.
J. Physiol. 128: 61, 1955.
15. USSING, H. H.: The use of tracers in the study
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Biol. 13: 193, 1948.
16. KEYNES, R. D., AND SWAN, R. C.: The effect
of external sodium concentration on the sodium
fluxes in frog skeletal muscle. J. Physiol. 147:
591, 1959.
17. HODGKIN, A. L., AND HOROWICZ, P.: The influence of potassium and chloride ions on the
membrane potential of single muscle fibres.
J. Physiol. 148: 127, 1959.
Circulation, Volume XX VI, November 1962
1223
18. ADRIAN, R. H.: Internal chloride concentration
and chloride efflux of frog muscle. J. Physiol.
156: 623, 1961.
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Movement of Inorganic Ions across the Membrane of Striated Muscle
R. H. ADRIAN
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Circulation. 1962;26:1214-1223
doi: 10.1161/01.CIR.26.5.1214
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