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Membrane E.M.F. changes under voltage clamp
Pergamon Preae
Iüe Scienoee, VoL 11 Part I, pp. 1175-1182, 1972 Printed in Great Bri~n
MEMBRANE E .M .F . CHANGES UNDER VOLTAGE CLAMP* R . De Benedettl and R . Lewis Department of Physics, University of Calgary Calgary, Alberta, Canada (Received 1 Augaat 1972; is Seal form 3 November 1972) SUMMARY The tibial branch of the desheathed sciatic nerve of the frog, Rang piptiena, has bean studied using the sucrose gap voltage clamp method . The current transient at the second step of command voltage is recorded and discussed in terms of some existing models of nerve action . When excitable cell membranes a m clamped at some value different from the holding potential, turning off the cornnand commonly results in an Instantaneous undershoot current which decays to zero within a few milliseconds .
The effect
has been Illustrated In experiments with squid axon (Cole, 1949 ; Tasaki and Spyropoulos, 1958), myelinated fibers of toad (Frankenhaeuser, 1962), Purkin]e fibers of frog atria (Haas et al ., 1971), Nitnlla (Ktshimoto, 1966), and uterine smooth muscle (Anderson, 1969) .
An example of such tails of current is shown for
frog nerve In Figure 1 .
The fact that the clamping current was non-zero after
the clamping potential
returned to the original resting potential, has been in-
terpreted as due to a change In the equivalent E .M .F . of the nerve during the applacation of a wnstant value command across the cell membrane at a value different from the holding potential .
This change In E .M .F . has been described in
terms of potassium Ion accumulation at the outside edge of the membrane (Frankenhaeuser and Hodgkin, 1956) for squid axon, and as a secondary Increase in sodium permeability for myellnated toad fibers (Frankenhaeuser, (1967) have proposed that improper voltage control
1962) .
Lecar et al .
is the source of such tails or
undershoots with the squid axon membrane, while Hille (1967) has suggested that In myellnated fibers, a lifting of the myelin around a node would account for the slow (10 meet) decay In leakage current, and thus the undershoot, by introducing *This investigation was supported by the National Research Council of Canada . 1175
Membrane E.M .F. ~ .
1176
voi . i ><, xo .u
a new resistance and capacitance in parallel with the original membrane equivalent circuit . In general, the tails following hyparpolarizlng commands have not been studied, while the w rrents elicited by such commands have simply been defined as leakage currant .
Since these undershoots appear to provide a reliable method of
measuring the membrane-generated E .M .F . Just prior to command turn-off, we used the method to determine the E .M .F . under a varlnty of conditions . Methods The nerve preparations ware the tibial branch of the desheathed sciatic nerve of the frog, Rana p~Lpiena . (Rud, 1961) .
These branches contain approximately 600 fibers
T.he nerves were kept in Ringer's at room temperature for at least
throe hours before use .
The nerve potentials were controlled by the double suc-
rose gap method which has been described previously by Lewis and Dtecke (1968), except that In these experiments the electrodes were corm~erctally available calomel cells .
All experiments were done at 25 ° C .
The Ringer's solution was made up of 113 mEq/1 NaCZ, 2 .5 mEq/1 KCZ, 2 .0 mEq/1 CaCZ a, and 2 .0 mEq/1 trls
(hydroxymethyl) amlnomethane (TRIS) buffer .
Choltns
chloride and potassium chloride replaced the sodium chloride to the preparation of the sodium-free and isotonic XCZ test solutions, respectively .
The concentra-
tion of the sucrose was 73 gm/1 with a measured resistivity greater than 500 I(>acm . When the voltage control was applied, the resting potential was operationally defined as that d .c . holding potential which resulted In zero current .
Two inde-
pendent square pulses were superimposed with a variable delay between them to supply any desired two-step command .
Ths voltage control system allowed the ap-
plication of a constant voltage stimulus to the nerve .
Measurements of membrane
E .M .F ., steady state current, initial aftershoot current, and electrical conductance were recorded as a function of the initial command voltage .
The voltage at
a second step In the command which yielded zero currant, after the fast capacitive
Vo1 .11, No . 24
II(embeane EM.F . mangea
spike, was defined as the membrane E .M .F . at that t1 me . were measured by superimposing small
1177
Electrical conductances
(1-2 mv) d .c . square pulses on the chosen
commands . Results All values for the membrane potentials (V) were referred to the resting potential and expressed In millivolts .
Thus V Is the magnitude of the command .
Due
to the uncertainty in the nodal membrane area, and the resulting unknown scaling factor, all values for membrane current ara expressed in arbitrary units . The vertical symmetry In the current response of the nerve to command magnitudes below threshold is displayed in Figure 2a .
At higher command values a
marked asymmetry was evident (Figure 2b) resulting to a maximum, constant under shoot for a wide range of depolarizing commands, while increasing hyperpolarizing commends yielded a linear Increase in the corresponding aftershoot current unless anode break occurred .
These results are sunmarized In Figure 3 .
If the mambrane generated E .M .F . had returned to its Initial value during the application of the square command, no aftershoot should have occurred when the command was terminated .
To determine the E .M .F . at the end of the command
period, a second command was used to repolarize the nodes to a potential which would glue zero current at the Instant of turnoff . initial
The difference between the
resting potential and the second conrnand potential is referred to as Vm ,
and Is plotted In Figure 4 .
It is noted the Vm saturates at about 10 my when the
initial caimands were depolarizing, but that hyperpolariztng commands elicit a linearly increasing magnitude for Vm .
The slope~of this Ilne depends on the tnt-
tlal command duration, as shown by the two sets of data . In comparing Figures 4 and 5 It was noted that the steep linear region of the steady state I-V curve corresponded to membrane with a constant maximum Vm , and a constant electrical conductance .
The subthreshold linear region of the I-V
curve, with a smaller slope, was associated with a linear variation of Vm as a function of the applied voltage and, again, a constant, though smaller, electrical conductance .
11~s
llE(cmurane E.11~.F.
r,
clv~
r"""
Vol. 11, No .24
~~~"
"""!~1
"""" """"
~"" ~
I
fi"""" "~~ "" ~
Figure 1 (a)
Clamping current for a depolarizing command .
(b)
Clamping currant for a hyperpolarizing command . (V ~ -40 mv) Vertical scales : current - 200 units/div . Horizontal stales : time - 10 msec/div .
(V ~ 40 mv)
"rr~-~-~"""" "~
\~i:"~! ~!" =~~ i
=~""""
Figure 2 (a)
Symmetry in subthreshold currant response . Clamping currants and associated aftershoots for commands V~10, 6, -6, -10 my from top to bottom . Vertical scale : current - 50 units/div . Horizontal scale : time - 10 msec/div . Nerve /140 . Clamping currents for commands from 13 to 53 my and - 13 to -53 mv . Note that all thn depolarizing commands share the same undershoot . Vertical scale : current - 500 units/div . Horizontal scale : time - 10 msec/div . Nerve #125 .
Membrane E.M .F .
Vo1.11, No . 24
1179
i 600 400 40 aa~c 700 30 -60
-50
-40
-30
-70
70
~~. .,~ ,~
-10
30
40
.....~~~~~
s0
60
~~ ...i..
-700
V ~~..
-aoo -600
Figura 3 Initial aftershoot current (l a ) versus Membrane potentlal (V) . There was no anode break excitation in the hyperpolarizing region . The bottom of the range fmr a constant undershoot was approximately 25 mv . Nerve äl40 .
30
â
70
10 -50
-40
-30
-70
-10
10
70
30
40
50
60
f_ 8 n~~c 4
r.T" r
-10
~
-70
-30
Figure 4 Membrane e .m .f . (Vm ) versus Membrane potentlal (V) . The data from which the broken line was plotted was recorded after 40 msec, while the solid line was recorded after 8 msec . Nerve äl41 .
V
Memlxane Fr.M.F . eba~a
i >< eo
voL i i, lvo.
u
w 1500
1000
40 os~o
500 -40
-30
-]0
V
-10 ~10
]0
I
-500
30
40
50
60
botto~ o! ranq~ !or ~ conitant utidurahoot.
-1000 Figura 5 Steady-state current (Iss) versus Manbrane potential ranges of constant and variable undershoot .
(V) .
Break to curve divides
When the holding potential was shifted to a depolarizing direction, a value was reached (approximately 25 my from resting potential) which abolished the undershoot
(measured relative to the new non-zero current baseline)
square turnoff trace after a depolarizing command .
resulting to a
A holding potential shift in
the hyperpolariztng direction simply increased the size of the relative undershoot In
response to a depolarizing command .
Neither shift significantly changed
the aftershoots following hyperpolarizing commands . were maintained An
All of these characteristics
in the sodium-free (cho rea) test solution .
Isotonic KCZ test solution did not eliminate the aftershoots nor did It
remove the constant undershoot effect . of the aftershoots were affected .
However,
the magnitudes and time constants
Furthermore, the time constants could be stg-
nificantly-modifted by varying the holding potential from the original
resting
potential (non-zero current baseline) to the new one at zero potential (zero current baseline) .
Time constants were 40 msec for undershoots following depolarlz-
ing corm~ands, and 10 msec for overshoots following hyperpolarizing eomnands, with both commands applied from the original
resting potential baseline .
applied in either direction from the zero potential baseline resulted
Cortmands in 5 msec
Membrane EMF. CäanBes
VoL 1Y, No. 24
time constants .
1181
The usual value In normal Ringer's, held at resting potential,
was 10 cosec with commands applied in either direction . Discussion While accumulation of potassium Ions on one side of the membrane during a long command would provide an undershoot which reached a maximum at higher depolarizing commands, It would contradict the existence of a syrtmatrical current response at subthreshold command values .
The substitution of choline for sodium,
while successfully maintaining the aftershoots and their properties, eliminates a secondary Increase In sodium permeability as a reasonable explanation .
The
simple Introduction of a new resistance and capacitance, as suggested by Hille, cannot simultaneously describe the symmetry In current response to low command values, as well as the saturation In the size of the undershoot at higher cormwnd values .
Furthermore no simple system of resistors and capacitors can expialn the
elimination of the undershoot by the application of a small d .c . biasing current . Thus, It is concluded that the undershoot is a manifestation of a real change in membrane E .M .F . rather than an apparent change supplied by non-msmbrene or by passive electrical effects .
This Interpretation of the undershoot is essentially
the same as that used by Tasakl and Haglwara (1957, see also Tasakl, 1968, p .
138)
for the squid giant axon, except that here we have shown the additional feature of an asynmntrlcal
response to cambnds of different polarities .
In comparing our results with the current traces shown for single myslinatsd fibers by Frankenhaeuser (1962, Figure 1), It appears as if a constant undershoot effect has occurred at 19, 38, and 57 nmr commands In normal Ringer's, and especi ally at 95, 114, and 133 my in 115 nm 3C1, with the holding potential set at the ordinary resting potential
In Ringer's .
Anderson (1969, Figure 9b) has apparently
obtained similar responses In uterine smooth muscle at turn-off, with the constant undershoot ôccurrlng after depolarization, and the Increasing undershoot following hyparpolarization .
It is, therefore, concluded that a maximum steady state V m
exists In the depolarizing direction, and that this maximum, as measured from the
Me®brane E.M.F. Q~anges
1182
Vol. 11, No.24
resting potential, Is tndnpendent of sodium or potassium concentration in the Ringer's solution .
The time course of the E .M .F . change does depend on the Ionic
environment as well as on the holding potential . References
(1969) : Voltage clamp studies on uterine smooth muscle . 54 : 145-165 .
Anderson, N .C .
Phbaiol .
J . Can.
(1949) : Dynamic electrical characteristics of the squid axon membrane . Aroh . Sai. Phbaiol. 3 : 253-258.
Cola, K .S .
Frankenhaeuser, B : (19626) : Instantaneous potassium currents in myellnated nerve fibres of Xenopua Zaevie . J. Physiol. 160 : 46-53 . Frankenhaeuser, B . 6 Hodgkin, A .L . (1956) : The after-effects of Impulses in the giant nerve fibres of LaZigo . J . PhbsioZ. 131 : 341-376 . Haas, H .G ., Kern, R ., Einwachter, H .M . 8 Tarr, M . (1971) : Kinetics of sodium Inactivation in frog atria . Pflugara Amh . ~: 141-157 . Hille, B . (1967) : The selective inhibition of delayed potassium currents in nerve by tetraethylamnonlum ton . J . Gen. PhysioZ. 50 : 1287-1302 . Klshimoto, U . (1966) : Voltage clamp and internal perfusion studies on NiteZla tnter~odes . J . Cell . Comp . Physiol. 66 : 43-54 . Lecar, H ., Ehrenstein, G ., Binstock, L . 8 Taylor, E . (1967) : Removal of potassium negative resistance in perfused squid giant axons . d . Gan. Phusiol. 50 : 1499 -
1515 .
Lewis R . 6 Dlecke, F .P .J . (1968) : Interactions of rubidium fluxes In frog nerve membrane . Life SaGenoea, Part 1 . 7 : 429-436 . Rud, J . (1961) : Low I anesthetics : An electrophystological Investigation of local anesthesia of peripheral nerves with special reference to xylocaine . Avta Physiol. Soaaui. vol . 51 supplementum 178 : 7-171 . Tasakl, I . (1968) : Nerve Excitation : A Macremolecular A Illinois, U .S .A ., Charles Thomas, pub Isher .
roach ; Springfield,
Tasakl, I . 6 Hagtwara, 5 . (1967) : Demonstration of two stable potential states In the squid giant axon under tetraethylammontum chloride . J. Can. PhyaioZ.
40 :
859-885.
Tasakl, I . b Spyropoulos, C .S . (1958) : Membrane conductance and current-voltage 193 : relation In the squid axon under voltage clamp . Amer . J. PhyaioZ.
318-327.
Iüe Scienoee, VoL 11 Part I, pp. 1175-1182, 1972 Printed in Great Bri~n
MEMBRANE E .M .F . CHANGES UNDER VOLTAGE CLAMP* R . De Benedettl and R . Lewis Department of Physics, University of Calgary Calgary, Alberta, Canada (Received 1 Augaat 1972; is Seal form 3 November 1972) SUMMARY The tibial branch of the desheathed sciatic nerve of the frog, Rang piptiena, has bean studied using the sucrose gap voltage clamp method . The current transient at the second step of command voltage is recorded and discussed in terms of some existing models of nerve action . When excitable cell membranes a m clamped at some value different from the holding potential, turning off the cornnand commonly results in an Instantaneous undershoot current which decays to zero within a few milliseconds .
The effect
has been Illustrated In experiments with squid axon (Cole, 1949 ; Tasaki and Spyropoulos, 1958), myelinated fibers of toad (Frankenhaeuser, 1962), Purkin]e fibers of frog atria (Haas et al ., 1971), Nitnlla (Ktshimoto, 1966), and uterine smooth muscle (Anderson, 1969) .
An example of such tails of current is shown for
frog nerve In Figure 1 .
The fact that the clamping current was non-zero after
the clamping potential
returned to the original resting potential, has been in-
terpreted as due to a change In the equivalent E .M .F . of the nerve during the applacation of a wnstant value command across the cell membrane at a value different from the holding potential .
This change In E .M .F . has been described in
terms of potassium Ion accumulation at the outside edge of the membrane (Frankenhaeuser and Hodgkin, 1956) for squid axon, and as a secondary Increase in sodium permeability for myellnated toad fibers (Frankenhaeuser, (1967) have proposed that improper voltage control
1962) .
Lecar et al .
is the source of such tails or
undershoots with the squid axon membrane, while Hille (1967) has suggested that In myellnated fibers, a lifting of the myelin around a node would account for the slow (10 meet) decay In leakage current, and thus the undershoot, by introducing *This investigation was supported by the National Research Council of Canada . 1175
Membrane E.M .F. ~ .
1176
voi . i ><, xo .u
a new resistance and capacitance in parallel with the original membrane equivalent circuit . In general, the tails following hyparpolarizlng commands have not been studied, while the w rrents elicited by such commands have simply been defined as leakage currant .
Since these undershoots appear to provide a reliable method of
measuring the membrane-generated E .M .F . Just prior to command turn-off, we used the method to determine the E .M .F . under a varlnty of conditions . Methods The nerve preparations ware the tibial branch of the desheathed sciatic nerve of the frog, Rana p~Lpiena . (Rud, 1961) .
These branches contain approximately 600 fibers
T.he nerves were kept in Ringer's at room temperature for at least
throe hours before use .
The nerve potentials were controlled by the double suc-
rose gap method which has been described previously by Lewis and Dtecke (1968), except that In these experiments the electrodes were corm~erctally available calomel cells .
All experiments were done at 25 ° C .
The Ringer's solution was made up of 113 mEq/1 NaCZ, 2 .5 mEq/1 KCZ, 2 .0 mEq/1 CaCZ a, and 2 .0 mEq/1 trls
(hydroxymethyl) amlnomethane (TRIS) buffer .
Choltns
chloride and potassium chloride replaced the sodium chloride to the preparation of the sodium-free and isotonic XCZ test solutions, respectively .
The concentra-
tion of the sucrose was 73 gm/1 with a measured resistivity greater than 500 I(>acm . When the voltage control was applied, the resting potential was operationally defined as that d .c . holding potential which resulted In zero current .
Two inde-
pendent square pulses were superimposed with a variable delay between them to supply any desired two-step command .
Ths voltage control system allowed the ap-
plication of a constant voltage stimulus to the nerve .
Measurements of membrane
E .M .F ., steady state current, initial aftershoot current, and electrical conductance were recorded as a function of the initial command voltage .
The voltage at
a second step In the command which yielded zero currant, after the fast capacitive
Vo1 .11, No . 24
II(embeane EM.F . mangea
spike, was defined as the membrane E .M .F . at that t1 me . were measured by superimposing small
1177
Electrical conductances
(1-2 mv) d .c . square pulses on the chosen
commands . Results All values for the membrane potentials (V) were referred to the resting potential and expressed In millivolts .
Thus V Is the magnitude of the command .
Due
to the uncertainty in the nodal membrane area, and the resulting unknown scaling factor, all values for membrane current ara expressed in arbitrary units . The vertical symmetry In the current response of the nerve to command magnitudes below threshold is displayed in Figure 2a .
At higher command values a
marked asymmetry was evident (Figure 2b) resulting to a maximum, constant under shoot for a wide range of depolarizing commands, while increasing hyperpolarizing commends yielded a linear Increase in the corresponding aftershoot current unless anode break occurred .
These results are sunmarized In Figure 3 .
If the mambrane generated E .M .F . had returned to its Initial value during the application of the square command, no aftershoot should have occurred when the command was terminated .
To determine the E .M .F . at the end of the command
period, a second command was used to repolarize the nodes to a potential which would glue zero current at the Instant of turnoff . initial
The difference between the
resting potential and the second conrnand potential is referred to as Vm ,
and Is plotted In Figure 4 .
It is noted the Vm saturates at about 10 my when the
initial caimands were depolarizing, but that hyperpolariztng commands elicit a linearly increasing magnitude for Vm .
The slope~of this Ilne depends on the tnt-
tlal command duration, as shown by the two sets of data . In comparing Figures 4 and 5 It was noted that the steep linear region of the steady state I-V curve corresponded to membrane with a constant maximum Vm , and a constant electrical conductance .
The subthreshold linear region of the I-V
curve, with a smaller slope, was associated with a linear variation of Vm as a function of the applied voltage and, again, a constant, though smaller, electrical conductance .
11~s
llE(cmurane E.11~.F.
r,
clv~
r"""
Vol. 11, No .24
~~~"
"""!~1
"""" """"
~"" ~
I
fi"""" "~~ "" ~
Figure 1 (a)
Clamping current for a depolarizing command .
(b)
Clamping currant for a hyperpolarizing command . (V ~ -40 mv) Vertical scales : current - 200 units/div . Horizontal stales : time - 10 msec/div .
(V ~ 40 mv)
"rr~-~-~"""" "~
\~i:"~! ~!" =~~ i
=~""""
Figure 2 (a)
Symmetry in subthreshold currant response . Clamping currants and associated aftershoots for commands V~10, 6, -6, -10 my from top to bottom . Vertical scale : current - 50 units/div . Horizontal scale : time - 10 msec/div . Nerve /140 . Clamping currents for commands from 13 to 53 my and - 13 to -53 mv . Note that all thn depolarizing commands share the same undershoot . Vertical scale : current - 500 units/div . Horizontal scale : time - 10 msec/div . Nerve #125 .
Membrane E.M .F .
Vo1.11, No . 24
1179
i 600 400 40 aa~c 700 30 -60
-50
-40
-30
-70
70
~~. .,~ ,~
-10
30
40
.....~~~~~
s0
60
~~ ...i..
-700
V ~~..
-aoo -600
Figura 3 Initial aftershoot current (l a ) versus Membrane potentlal (V) . There was no anode break excitation in the hyperpolarizing region . The bottom of the range fmr a constant undershoot was approximately 25 mv . Nerve äl40 .
30
â
70
10 -50
-40
-30
-70
-10
10
70
30
40
50
60
f_ 8 n~~c 4
r.T" r
-10
~
-70
-30
Figure 4 Membrane e .m .f . (Vm ) versus Membrane potentlal (V) . The data from which the broken line was plotted was recorded after 40 msec, while the solid line was recorded after 8 msec . Nerve äl41 .
V
Memlxane Fr.M.F . eba~a
i >< eo
voL i i, lvo.
u
w 1500
1000
40 os~o
500 -40
-30
-]0
V
-10 ~10
]0
I
-500
30
40
50
60
botto~ o! ranq~ !or ~ conitant utidurahoot.
-1000 Figura 5 Steady-state current (Iss) versus Manbrane potential ranges of constant and variable undershoot .
(V) .
Break to curve divides
When the holding potential was shifted to a depolarizing direction, a value was reached (approximately 25 my from resting potential) which abolished the undershoot
(measured relative to the new non-zero current baseline)
square turnoff trace after a depolarizing command .
resulting to a
A holding potential shift in
the hyperpolariztng direction simply increased the size of the relative undershoot In
response to a depolarizing command .
Neither shift significantly changed
the aftershoots following hyperpolarizing commands . were maintained An
All of these characteristics
in the sodium-free (cho rea) test solution .
Isotonic KCZ test solution did not eliminate the aftershoots nor did It
remove the constant undershoot effect . of the aftershoots were affected .
However,
the magnitudes and time constants
Furthermore, the time constants could be stg-
nificantly-modifted by varying the holding potential from the original
resting
potential (non-zero current baseline) to the new one at zero potential (zero current baseline) .
Time constants were 40 msec for undershoots following depolarlz-
ing corm~ands, and 10 msec for overshoots following hyperpolarizing eomnands, with both commands applied from the original
resting potential baseline .
applied in either direction from the zero potential baseline resulted
Cortmands in 5 msec
Membrane EMF. CäanBes
VoL 1Y, No. 24
time constants .
1181
The usual value In normal Ringer's, held at resting potential,
was 10 cosec with commands applied in either direction . Discussion While accumulation of potassium Ions on one side of the membrane during a long command would provide an undershoot which reached a maximum at higher depolarizing commands, It would contradict the existence of a syrtmatrical current response at subthreshold command values .
The substitution of choline for sodium,
while successfully maintaining the aftershoots and their properties, eliminates a secondary Increase In sodium permeability as a reasonable explanation .
The
simple Introduction of a new resistance and capacitance, as suggested by Hille, cannot simultaneously describe the symmetry In current response to low command values, as well as the saturation In the size of the undershoot at higher cormwnd values .
Furthermore no simple system of resistors and capacitors can expialn the
elimination of the undershoot by the application of a small d .c . biasing current . Thus, It is concluded that the undershoot is a manifestation of a real change in membrane E .M .F . rather than an apparent change supplied by non-msmbrene or by passive electrical effects .
This Interpretation of the undershoot is essentially
the same as that used by Tasakl and Haglwara (1957, see also Tasakl, 1968, p .
138)
for the squid giant axon, except that here we have shown the additional feature of an asynmntrlcal
response to cambnds of different polarities .
In comparing our results with the current traces shown for single myslinatsd fibers by Frankenhaeuser (1962, Figure 1), It appears as if a constant undershoot effect has occurred at 19, 38, and 57 nmr commands In normal Ringer's, and especi ally at 95, 114, and 133 my in 115 nm 3C1, with the holding potential set at the ordinary resting potential
In Ringer's .
Anderson (1969, Figure 9b) has apparently
obtained similar responses In uterine smooth muscle at turn-off, with the constant undershoot ôccurrlng after depolarization, and the Increasing undershoot following hyparpolarization .
It is, therefore, concluded that a maximum steady state V m
exists In the depolarizing direction, and that this maximum, as measured from the
Me®brane E.M.F. Q~anges
1182
Vol. 11, No.24
resting potential, Is tndnpendent of sodium or potassium concentration in the Ringer's solution .
The time course of the E .M .F . change does depend on the Ionic
environment as well as on the holding potential . References
(1969) : Voltage clamp studies on uterine smooth muscle . 54 : 145-165 .
Anderson, N .C .
Phbaiol .
J . Can.
(1949) : Dynamic electrical characteristics of the squid axon membrane . Aroh . Sai. Phbaiol. 3 : 253-258.
Cola, K .S .
Frankenhaeuser, B : (19626) : Instantaneous potassium currents in myellnated nerve fibres of Xenopua Zaevie . J. Physiol. 160 : 46-53 . Frankenhaeuser, B . 6 Hodgkin, A .L . (1956) : The after-effects of Impulses in the giant nerve fibres of LaZigo . J . PhbsioZ. 131 : 341-376 . Haas, H .G ., Kern, R ., Einwachter, H .M . 8 Tarr, M . (1971) : Kinetics of sodium Inactivation in frog atria . Pflugara Amh . ~: 141-157 . Hille, B . (1967) : The selective inhibition of delayed potassium currents in nerve by tetraethylamnonlum ton . J . Gen. PhysioZ. 50 : 1287-1302 . Klshimoto, U . (1966) : Voltage clamp and internal perfusion studies on NiteZla tnter~odes . J . Cell . Comp . Physiol. 66 : 43-54 . Lecar, H ., Ehrenstein, G ., Binstock, L . 8 Taylor, E . (1967) : Removal of potassium negative resistance in perfused squid giant axons . d . Gan. Phusiol. 50 : 1499 -
1515 .
Lewis R . 6 Dlecke, F .P .J . (1968) : Interactions of rubidium fluxes In frog nerve membrane . Life SaGenoea, Part 1 . 7 : 429-436 . Rud, J . (1961) : Low I anesthetics : An electrophystological Investigation of local anesthesia of peripheral nerves with special reference to xylocaine . Avta Physiol. Soaaui. vol . 51 supplementum 178 : 7-171 . Tasakl, I . (1968) : Nerve Excitation : A Macremolecular A Illinois, U .S .A ., Charles Thomas, pub Isher .
roach ; Springfield,
Tasakl, I . 6 Hagtwara, 5 . (1967) : Demonstration of two stable potential states In the squid giant axon under tetraethylammontum chloride . J. Can. PhyaioZ.
40 :
859-885.
Tasakl, I . b Spyropoulos, C .S . (1958) : Membrane conductance and current-voltage 193 : relation In the squid axon under voltage clamp . Amer . J. PhyaioZ.
318-327.