Article

Tge control of membrane ionic currents by the membrane potential of muscle

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Abstract

Comparisons between electrotronic potentials and certain predicted curves allow the identification of the membrane potential at which the sodium and potassium currents are switched on in frog sartorius. The activation potentials (the membrane potentials at which the ionic currents are great enough to be resolved by the method) are functions of the resting potential and time but not of ionic concentration. In the normal fiber, the activation potential for sodium lies nearer the resting potential and depolarizations set off sodium currents and action potentials. Below a resting potential of 55 to 60 mv. sodium activation is lost and conduction is impossible. A tenfold increase of calcium concentration lowers (moves further from the resting potential) the sodium activation potential by 20 to 25 mv. whereas the potassium activation potential is lowered by only 15 mv. Certain consequences of this are seen in the behavior of the muscle cell when it is stimulated with long duration shock.

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... Fenn and Cobb (1936) on rat muscles, and Hodgldn and Horowicz (1959 a) on frog skeletal muscles observed the release of potassium ion with muscle activity, suggesting an increase in K permeability during the repolarization phase of the action potential. Jenerick (1953Jenerick ( , 1959 reported the existence of delayed rectification in the skeletal muscle fiber, and Narahashi et al. (1960) observed the occurrence of delayed rectification in muscle rendered inexcitable with tetrodotoxin, a toxic substance obtained from the puffer. ...
... This result partly coincides with J e nerick's observation (1959). The potential indicated by the arrow a in Fig. 1 is the potassium activation potential defined by Jenerick (1959). This is the potential at which delayed rectification becomes first noticeable. ...
... It was shown, confirming the observations made by Jenerick (1953Jenerick ( , 1959 and by Narashashi et al. (1960), that delayed rectification occurred also in the skeletal muscle membrane. Since it was elicited for the muscle bathed in the Na2SO4 and K2SO4 solution as well as in choline-Ringer's solution and normal Ringer's solution with tetrodotoxin, it seems reasonable to assume that, as in the squid giant axon (Hodgkin, Huxley, and Katz, 1949), the delayed rectification is indicative of an increase in the potassium conductance which occurs upon depolarization. ...
Article
Delayed rectification was elicited in frog's skeletal muscles bathed in choline-Ringer's solution, in normal Ringer's solution with tetrodotoxin, in 40 mM Na2SO4 solution with tetrodotoxin, and even in 40 mM K2SO4 solution when the membrane had been previously hyperpolarized. However, after a sustained depolarization current-voltage relations in 40 mM K2SO4 and in 40 mM Na2SO4 solutions revealed a rectifier property in the anomalous direction. This indicates that the increase in potassium conductance which is brought about upon depolarization is a transient phenomenon and is inactivated by a maintained depolarization, and that this potassium inactivation process converts the delayed rectification into the anomalous rectification. In normal Ringer's solution with tetrodotoxin and in the 40 mM Na2SO4 solution with tetrodotoxin the apparent resistance was increased when the membrane was hyperpolarized beyond about -150 mv. This is thought to be due to a decrease of K conductance caused by a strong hyperpolarizing current. In the 40 mM Na2SO4 solution with tetrodotoxin a de- or hyperpolarizing current pulse induced a prolonged depolarizing response. During the early phase of this response the effective resistance was lower, and during the following phase greater than that in the resting fiber. An interpretation in terms of the ionic hypothesis was made of the nature of this response.
... If either the K + conductance at rest were sufficiently high or if the increase triggered by activity occurred early enough, the regenerative response initiated by inward movement of Na + would produce only a highly damped action potential. In this connection, it is of interest that frog muscle possesses the safety factor of a lower threshold for regenerative Na + conductance than is that for activation of K t conductance (18). If high K + conductance were responsible for graded responsiveness, K inactivation (10,12) or merely passive blockage of potassium valves by the alkali-earth cations would lead to far larger action potentials. ...
Article
Graded electrically excited responsiveness of Romalea muscle fibers is converted to all-or-none activity by Ba⁺⁺, Sr⁺⁺, or Ca⁺⁺, the two former being much the more effective in this action. The change occurs with as little as 7 to 10 per cent of Na⁺ substituted by Ba⁺⁺. The spikes now produced have overshoots and may be extremely prolonged, lasting many seconds. During the spike the membrane resistance is lower than in the resting fiber, but the resting resistance and time constant are considerably increased by the alkali-earth ions. The excitability is also increased, spikes arising neurogenically from spontaneous repetitive discharges in the axon as well as myogenically from spontaneous activity in the muscle fibers. Repetitive responses frequently occur on intracellular stimulation with a brief pulse. The data indicate that the alkali-earth ions exert a complex of effects on the different action components of electrically excitable membrane. They may be described in terms of the ionic theory as follows: The resting K⁺ conductance is diminished. The sodium inactivation process is also diminished, and sodium activation may be increased. Together these changes can act to convert graded responsiveness to the all-or-none variety. The alkali-earth ions can also to some degree carry inward positive charge during activity, since spikes are produced when Na⁺ is fully replaced with the divalent ions.
... This seems to be a consequence of the elevated ammonia concentrations in these fish. This, in turn, may influence swimming performance by inactivating voltage-gated Na + channels and causing a subsequent loss of electrical excitability in these muscle fibres (Jenerick, 1959). A similar phenomenon could account for the absence of white muscle recruitment in trout exposed to sublethal low pH, swimming at speeds at which such recruitment = × , [Tamm]i [Tamm]e ([H + ]i + K) ...
Article
Previously, the distribution of ammonia between the intracellular and extracellular compartments has been used to predict a significant depolarisation of the resting membrane potential (E(M)) of white muscle from brown trout (Salmo trutta) exposed to a sub-lethal combination of copper and low pH. However, this prediction is based upon two assumptions (i) a relatively high membrane permeability for the ammonium ion with respect to that for ammonia gas and (ii) that this is unaltered by exposure to copper and low pH. Since there is conflicting evidence in the literature of the validity of these assumptions, in the present study E(M) was directly measured in white muscle fibres of trout exposed to copper and low pH (E(M)=-52.2+/-4.9 mV) and compared with that of unexposed, control animals (E(M)=-86.5+/-2.9 mV) (means +/- s.e.m., N=6). In confirming the predicted depolarisation, these data support the hypothesis of electrophysiological impairment as a factor in the reduction in the swimming performance of trout exposed to these pollutants. In addition, the results of this study support the role of a significant permeability of the muscle membrane to NH(4)(+) in determining the distribution of ammonia in fish.
... If either the K + conductance at rest were sufficiently high or if the increase triggered by activity occurred early enough, the regenerative response initiated by inward movement of Na + would produce only a highly damped action potential. In this connection, it is of interest that frog muscle possesses the safety factor of a lower threshold for regenerative Na + conductance than is that for activation of K t conductance (18). If high K + conductance were responsible for graded responsiveness, K inactivation (10,12) or merely passive blockage of potassium valves by the alkali-earth cations would lead to far larger action potentials. ...
Article
Graded electrically excited responsiveness of Romalea muscle fibers is converted to all-or-none activity by Ba++, Sr++, or Ca++, the two former being much the more effective in this action. The change occurs with as little as 7 to 10 per cent of Na+ substituted by Ba++. The spikes now produced have overshoots and may be extremely prolonged, lasting many seconds. During the spike the membrane resistance is lower than in the resting fiber, but the resting resistance and time constant are considerably increased by the alkali-earth ions. The excitability is also increased, spikes arising neurogenically from spontaneous repetitive discharges in the axon as well as myogenically from spontaneous activity in the muscle fibers. Repetitive responses frequently occur on intracellular stimulation with a brief pulse. The data indicate that the alkali-earth ions exert a complex of effects on the different action components of electrically excitable membrane. They may be described in terms of the ionic theory as follows: The resting K+ conductance is diminished. The sodium inactivation process is also diminished, and sodium activation may be increased. Together these changes can act to convert graded responsiveness to the all-or-none variety. The alkali-earth ions can also to some degree carry inward positive charge during activity, since spikes are produced when Na+ is fully replaced with the divalent ions.
... In Purkinje fibers, as in other excitable tissues, calcium and various other cations produce voltage shifts in the kinetic variables (e.g. Weidmann, 1955;Frankenhaeuser and Hodgkin, 1957;Jenerick, 1959). In the specific case of iK,, increasing [Ca] 0 fourfold shifts the activation curve by about 8 mV ( Noble and Tsien, unpublished;Brown, 1973). ...
Article
Hauswirth et al. (1968) proposed that epinephrine acts on i(KK2) by adding its own positive charge to the external membrane surface near the i(KK2) channel. This hypothesis was tested by using noncationic compounds, theophylline and R07-2956, which mimicked epinephrine's effects on pacemaker activity and on i(KK2). In maximally effective doses, theophylline or R07-2956 occluded the effect of epinephrine, indicating a shared final common mechanism. Since theophylline and R07-2956 are noncationic at pH 7.4, the common mechanism cannot be a direct change in external surface charge. On the contrary, epinephrine does not interfere with the voltage shift produced by La(+++), which is thought to modify the external surface charge. The results argue against the original hypothesis but leave open the possibility that an alteration in internal surface charge generates the observed voltage shift. The potency of theophylline and R07-2956 as phosphodiesterase inhibitors suggests that the final common mechanism begins with the elevation of intracellular cyclic AMP, leading to a saturable process which limits the voltage shift's magnitude. This hypothesis is used to generate dose-response curves describing the combined effects of epinephrine and theophylline, and these are compared with experimental data.
... Dittgau (1963) and Caputo & Gimenez (1967) have shown that removal of external Ca2+ in twitch fibres produces membrane depolarization, whereas raising Ca2+ hyperpolarizes frog twitch muscle fibres, but not slow (Stefani & Steinbach, 1969). Calcium and magnesium ions are also known to affect conductance change thresholds in twitch muscle fibres (Jenerick, 1959;Costantin, 1968) and contraction threshold in the muscle cells (Costantin, 1968). ...
Article
1. The ultrastructure of adult pigeon iris muscle fibres has been described with emphasis on the distribution of the sarcoplasmic reticulum (SR). Contractures due to superfusion with solutions of different [K(+)] (3-150 mM) and acetylcholine (ACh) and their modification by alteration of external [Ca(2+)] and [Mg(2+)] were studied in isolated pigeon iris.2. The arrangement of the contractile myofilaments was like that of vertebrate skeletal fibres. The SR is well developed in the I-band and sparse at the A-band level. Tubular elements (T-system) which form triads with the SR were seen at all levels of the sarcomere though usually adjacent to the A-I junction.3. K(+) contractures developed monotonically to a steady level which was maintained for the duration of the high [K(+)] superfusion. The response to a standard [K(+)] stepwise change was not altered by conditioning the preparation with various [K(+)].4. Decreasing external [Ca(2+)] from 20 mM to Ca(2+)-free (i.e. no Ca(2+) added), enhanced iris contractures at all [K(+)] and in ACh enriched solutions. The K(+) response was abolished when the iris was superfused with Ca(2+) free solution plus EDTA (2 mM) for 45 min. Increasing [Mg(2+)] had little or no effect on iris contracture.5. Reducing external [Ca(2+)] from 3 to 0.3 mM caused a reduction of 3-7 mV in resting membrane potential and an increase from 3 to 10 mM-Ca(2+) caused 3 to 7 mV membrane hyperpolarization. Muscle fibre input resistance was not affected.6. It is concluded that in the pigeon iris, Ca(2+) required for contractile activation is obtained from internal stores, that membrane potential determines the degree of contractile activation and that the maintenance of the contracture is dependent on the failure of the Ca(2+) releasing mechanism to inactive. In addition, it is speculated that because the iris muscle has only sparse SR at the A-band level of the sarcomere, there may be slow Ca(2+) reaccumulation.
... In Purkinje fibers, as in other excitable tissues, calcium and various other cations produce voltage shifts in the kinetic variables (e.g. Weidmann, 1955;Frankenhaeuser and Hodgkin, 1957;Frankenhaeuser, 1957;Jenerick, 1959). In the specific case of iK,, increasing [Ca] 0 fourfold shifts the activation curve by about 8 mV (Noble and Tsien, unpublished;Brown, 1973). ...
Article
Hauswirth et al. (1968) proposed that epinephrine acts on iKK2 by adding its own positive charge to the external membrane surface near the iKK2 channel. This hypothesis was tested by using noncationic compounds, theophylline and R07-2956, which mimicked epinephrine's effects on pacemaker activity and on iKK2. In maximally effective doses, theophylline or R07-2956 occluded the effect of epinephrine, indicating a shared final common mechanism. Since theophylline and R07-2956 are noncationic at pH 7.4, the common mechanism cannot be a direct change in external surface charge. On the contrary, epinephrine does not interfere with the voltage shift produced by La+++, which is thought to modify the external surface charge. The results argue against the original hypothesis but leave open the possibility that an alteration in internal surface charge generates the observed voltage shift. The potency of theophylline and R07-2956 as phosphodiesterase inhibitors suggests that the final common mechanism begins with the elevation of intracellular cyclic AMP, leading to a saturable process which limits the voltage shift's magnitude. This hypothesis is used to generate dose-response curves describing the combined effects of epinephrine and theophylline, and these are compared with experimental data.
Article
Delayed rectification was elicited in frog's skeletal muscles bathed in choline-Ringer's solution, in normal Ringer's solution with tetrodotoxin, in 40 mM Na(2)SO(4) solution with tetrodotoxin, and even in 40 mM K(2)SO(4) solution when the membrane had been previously hyperpolarized. However, after a sustained depolarization current-voltage relations in 40 mM K(2)SO(4) and in 40 mM Na(2)SO(4) solutions revealed a rectifier property in the anomalous direction. This indicates that the increase in potassium conductance which is brought about upon depolarization is a transient phenomenon and is inactivated by a maintained depolarization, and that this potassium inactivation process converts the delayed rectification into the anomalous rectification. In normal Ringer's solution with tetrodotoxin and in the 40 mM Na(2)SO(4) solution with tetrodotoxin the apparent resistance was increased when the membrane was hyperpolarized beyond about -150 mv. This is thought to be due to a decrease of K conductance caused by a strong hyperpolarizing current. In the 40 mM Na(2)SO(4) solution with tetrodotoxin a de- or hyperpolarizing current pulse induced a prolonged depolarizing response. During the early phase of this response the effective resistance was lower, and during the following phase greater than that in the resting fiber. An interpretation in terms of the ionic hypothesis was made of the nature of this response.
Article
The effects of ethanol on the membrane potential and membrane resistance of frog muscle fibres in vitro were studied by means of intracellular microelectrode technique. By continuous recording of the membrane potential level from one fibre, as well as by consecutive recordings from different fibres, the time course of the potential changes induced by different concentrations of ethanol was followed for periods of up to one hour. At the lowest concentrations used, 0.05 and 0.1 M, a depolarization, although slow and sometimes irregular, could usually be demonstrated. At a concentration equal to or higher than 0.2 M, a marked lowering of the membrane potential value was regularly observed. The depolarization rate increased with higher ethanol content, a typical result being a 15 per cent reduction of the initial membrane potential value after 15 min of exposure to 1.0 M ethanol. Reversal of the membrane potential changes after the ethanol had been washed out from the muscle bath was also demonstrated. Determinations of the voltage-current relation of the muscle fibre, either by square pulse analysis or by direct recording of voltage-current curves, revealed a gradual lowering of the membrane resistance, the effect increasing with the ethanol concentration from 0.2 to 1.0 M; at lower concentrations the changes in membrane resistance were within the normal variations found in untreated muscle.
Article
A method is presented for determining the magnitude of the ionic current associated with the propagated spike potential. Parameters of the action current are then compared to various aspects of the response as recorded in a phase plane. The findings also include evidence for (a) Na(+) ion as the major inward current carrier, (b) a fairly constant membrane conductance during the terminal phase ( approximately 1 msec.) of the spike potential, and (c) the influence of Ca(++) ion concentration on the action current.
Article
Full-text available
Local anesthetics have been found to act as competitive inhibitors of caffeine in frog sartorius muscle. They block caffeine-induced rigor and the attendant increase in Ca(45) influx and efflux. Increased net uptake of sodium, loss of potassium, and concurrent increase in oxygen consumption are all effectively blocked by procaine. Evidence is presented that the inhibitory effect of the local anesthetics cannot be explained by the formation of molecular complexes with caffeine. Increased efflux of Ca(45) produced by changing from zero calcium Ringer's to 0.1 mM or 1 mM calcium Ringer's is inhibited by procaine and tetracaine. EDTA-stimulated calcium efflux is not affected by either local anesthetic. Caffeine rigor develops in frog muscle depolarized with KCl or rendered electrically inexcitable by sodium lack. Both the rigor and the increased calcium fluxes are inhibited by local anesthetics in depolarized muscle.
Article
Conversion of graded responsiveness of lobster muscle fibers to all-or-none activity by alkali-earth and tetraethylammonium (TEA) ions appears to be due to a combination of effects. The membrane is hyperpolarized, its resistance is increased, and its sensitivity to external K(+) is diminished, all effects which indicate diminished K(+) conductance. While the spikes are prolonged, the conductance is higher throughout the response than it is in the resting membrane. Repetitive activity becomes prominent. These effects indicate maintained high conductance for an ion which causes depolarization. This is normally Na(+), since its presence in low concentrations potentiates the effects of Ba(++), but the alkali-earth ions and TEA can also carry inward charge. Ba(++), Sr(++), and TEA appear to be more effective than is Ca(++) in its normal role, which is probably to depress K(+) conductance and Na inactivation. Thus, conversion of graded to all-or-none responsiveness appears to occur because of the relative increase of depolarizing inward ion flux and decrease of repolarizing outward flux.
Article
Graded electrically excited responsiveness of Romalea muscle fibers is converted to all-or-none activity by Ba(++), Sr(++), or Ca(++), the two former being much the more effective in this action. The change occurs with as little as 7 to 10 per cent of Na(+) substituted by Ba(++). The spikes now produced have overshoots and may be extremely prolonged, lasting many seconds. During the spike the membrane resistance is lower than in the resting fiber, but the resting resistance and time constant are considerably increased by the alkali-earth ions. The excitability is also increased, spikes arising neurogenically from spontaneous repetitive discharges in the axon as well as myogenically from spontaneous activity in the muscle fibers. Repetitive responses frequently occur on intracellular stimulation with a brief pulse. The data indicate that the alkali-earth ions exert a complex of effects on the different action components of electrically excitable membrane. They may be described in terms of the ionic theory as follows: The resting K(+) conductance is diminished. The sodium inactivation process is also diminished, and sodium activation may be increased. Together these changes can act to convert graded responsiveness to the all-or-none variety. The alkali-earth ions can also to some degree carry inward positive charge during activity, since spikes are produced when Na(+) is fully replaced with the divalent ions.
Article
Brown trout acclimated to soft water and exposed for 96 h to a sub-lethal concentration of copper at low pH (0.08 micromol l(-1) Cu, pH 5) have a lower critical swimming speed than fish from copper-free water at neutral pH. This loss of performance is not due to difficulties in oxygen transfer resulting from gill damage since arterial oxygen and carbon dioxide levels remain unaffected. Both red and white muscle showed some metabolic disruptions consistent with local hypoxia, namely a high lactate concentration at rest and, in the white muscle, depletion of glycogen and phosphocreatine. However, a putative role of increased blood viscosity following haematological changes in reducing the supply of oxygen to the tissues is not supported by the current study. Haematocrit, haemoglobin and plasma protein concentrations were not affected by this treatment and a lack of further change in variables such as lactate at the onset of exercise led one to look for an alternative explanation for the effects of copper and low pH upon tissue metabolites. Ammonia concentration, both in the plasma and muscles, is significantly higher in trout exposed to copper and low pH. Ammonia plays a role in the regulation of a number of metabolic pathways and could contribute to the altered metabolic status of these fish. In addition, ammonium ions are known to cause electrophysiological disruptions, particularly the displacement of K(+) in ion exchange mechanisms that could lead to the observed loss of swimming performance. Using the measured distribution of ammonia between intracellular and extracellular compartments to estimate membrane potential of resting muscle, a significant depolarisation is predicted in both red and white muscle of fish exposed to copper and low pH.
Article
1. Contractile responses in short twitch-type snake muscle fibres have been studied. These fibres are sufficiently short to allow fairly uniform changes in membrane potential along their length when current is passed through an intracellular micropipette. Active sodium permeability changes were blocked with tetrodotoxin (TTX), procaine, or by using solutions low in sodium. Current and voltage micropipettes were used to voltage-clamp these fibres. Depolarization steps to about -40 mV evoked contractile responses, maximal tension being developed between -10 and 0 mV. The relation between contraction and membrane potential was sigmoid.2. Depolarization beyond a critical threshold produced an increment of outward current which inactivated with time. The threshold for this delayed rectification was normally similar to the threshold for contractile activation. Fibres exposed to high potassium showed a reversal of this inactivating current to slightly super-threshold depolarizing pulses. At membrane potentials near 0 mV, no inactivating current was noted, while stronger depolarizing pulses produced an inactivating current in the normal direction. Fibres in high potassium show the same threshold for initiation of contraction as in normal solution.3. Thiocyanate, nitrate, and caffeine shifted the relation between membrane potential and contraction toward higher levels of membrane potential. The threshold for inactivating rectifying current failed to shift to a corresponding extent, although some shift in rectification which did not inactivate was evident.4. When depolarization was maintained, contractile tension was maximal for several seconds, then gradually disappeared. The rate of this contractile inactivation depended upon the level of depolarization.
Article
Compound muscle action potential (CMAP) amplitudes, response to 2 Hz nerve stimulation, response to exercise and electromyographic needle electrode examination findings from the thenar muscles of two patients with paramyotonia congenita were compared with those from two patients with dominantly inherited myotonia congenita in warm (34 degrees C) and cold (20 degrees C) states. Cold induced a significant fall in CMAP amplitude, induced/worsened a significant decremental response to 2 Hz stimulation, and virtually abolished myotonia and voluntary recruitment of motor unit potentials in patients with paramyotonia congenita; none of these occurred in myotonia congenita. Though exercise induced a mild fall in CMAP amplitude in both groups, postexercise fibrillations occurred only in patients with paramyotonia congenita. These findings serve to distinguish these two entities in the clinical electromyography laboratory.
Article
1. The actions of three saxitoxin (STX) analogues have been studied on the frog sartorius muscle fibre and the squid giant axon. One--neosaxitoxin--is a natural analogue, and two--decarbamylsaxitoxin and reduced saxitoxin--are synthetic. 2. The maximum dV/dt of the action potential in paired-muscle protocol is reduced by the analogues with relative potencies: STX (1), tetrodotoxin (1), neo-STX (1), decarbamyl-STX (0.2) and reduced-STX (0.01). 3. In constant-current studies on frog muscle fibres and in voltage-clamp studies on squid axons, all three analogues block only the sodium channel without affecting the potassium channel. 4. All three analogues bind to the same site as does STX in a competitive manner. 5. The experimental results suggest that the active groups in STX are the 7,8,9 guanidinium and the C-12 hydroxy groups. The carbamyl group contributes to, but is not essential for activity. 6. Stereospecific groups in the tetrodotoxin (TTX) molecule are the 1,2,3 guanidinium and the C-9, C-10 hydroxy groups. C-4 and C-8 groups are also important. 7. As new view is proposed in which STX and TTX can bind to a receptor located in the outside surface of the membrane very close to the orifice of the sodium channel.
Article
1. The effect of extracellular calcium and magnesium on the contraction threshold and on the thresholds for an increase in sodium and potassium conductance with depolarization was studied in voltage-clamped frog muscle fibres.2. A larger depolarization was required to reach each of the three thresholds when the concentration of divalent cation was increased.3. The contraction and potassium conductance thresholds appeared to shift in parallel with alterations in calcium over the concentration range 0.2-10.0 mM and in magnesium over the concentration range 5.4-90.0 mM. The shift amounted to about 4 mV for a threefold change in concentration of divalent cation.4. The sodium conductance threshold was much more sensitive to alterations in divalent cation concentration than was either the contraction or the potassium conductance threshold.
Article
1.Changes in membrane potential of frog skeletal muscle fibres (m. iliofibularis) due to alternating current (ac) up to 10 kHz and direct current (dc) are recorded with two intracellular microelectrodes.2.Stimulation by ac with frequencies above 500 Hz induces a mean depolarization $$\bar Vm{\text{ }} \bullet {\text{ }}\bar Vm$$ depends in a small range on the strength of the ac stimulus, and reaches a maximum of about 50 mV with stronger currents. When related to the absolute membrane potentialEm, this maximum $$(\bar E_m )max = E_m + (\bar Vm)max = - 45 mV$$ is hardly affected by alterations ofEm; below a membrane potential of -45 mV the depolarizing effect of ac stimulation is negligible.3.The mean depolarization $$\bar V_m $$ is explained mainly by rectification in the sodium channel; this interpretation is proved by the almost complete abolition of $$\bar V_m $$ in sodium free solution or in Ringer's solution containing tetrodotoxin 10-7 g/ml. A slight residual amount of $$\bar V_m $$ may be caused by anomalous rectification in the potassium system, as indicated by experiments in tetraethylammonium chloride 60 mM/l.4.Ac and dc stimulation above threshold strength induce repetitive activity with trains of action potentials. The subsequent spikes are higher, the critical prepotentials are lower, and the time intervals are shorter with ac than with dc.5.These facts agree, in principle, with findings on the nodal membrane; small differences may be attributed to anomalous rectification.
Article
The motor endplate of frog sartorius muscle was voltage clamped and the peak current to different concentrations of acetylcholine and carbachol applied in the perfusing fluid was measured. Perfusing fluid was hypertonic in order to suppress contractions. Current responses were smooth and reached a peak value within 2-5 s. The dose-response curve was usually linear even with concentrations of 10(-2) M acetylcholine, indicating that the conductance change was probably proportional to the concentration of acetylcholine or carbachol. With high concentrations nonlinearity sometimes appeared but in these cases the fast onset of desensitization appeared to be preventing the current response from reaching its expected peak amplitude. When the depolarization produced by acetylcholine in a non-voltage-clamped endplate was measured the dose-response curve was hyperbolic. This relationship was imposed by the electrical properties of the endplate membrane and its surrounding sarcolemma, and could be predicted if the input resistance of the fiber was known. Experiments were also done on slow muscle fibers. Depolarizing analogues of acetylcholine had similar effects to acetylcholine. d-Tubocurarine reduced the proportionality constant between concentration of acetylcholine and conductance change, and this resulted in a parallel shift of the log-concentration depolarization curve. A linear dose-response curve was unexpected within the context of current theories of drug action.
Article
Changes in membrane potential of single frog motor nerve fibres due to alternating current (ac) between 4 kHz and 20 kHz were recorded in the air gap equipment under constant current conditions at 20°C. The experimental findings were compared with the results of computations on the basis of potential clamp data. Ac shifted mean membrane potential (averaged for every ac period) in the direction of depolarization. The mean depolarizationV m depended on current strengthI; it disappeared when the sodium permeability was blocked, in the experiments by tetrodotoxin. In a current range between about 1 and 3 fold threshold strength the ac initiated repetitive activity with response frequencies ν between averaged 120 Hz and 820 Hz or in the computations even higher; ν depended logarithmically on current strength, but was independent of ac frequency. Elimination of current amplitudeI from the nonlinear relations ν (I) andV m (I) led to a linear function between ν andV m. Both ν andV m depended markedly on prepolarization of the node. The results were attributed to the preferred activation of the sodium permeability under maintained high frequency ac stimulation. Differences between computations and constant current experiments occurred for very long stimulus duration when rhythmical discharges died out in the experiment.
Article
Intracellular electrodes were used for studying the responses of frog muscle fibers to linearly rising currents over a wide range of gradients (0.4–400 μA/sec) corresponding to spike latencies up to 1 sec. In fibers with normal resting potential the critical firing level showed no significant variations at different gradients. With lowering of the gradient there was a successive decrease in stimulus threshold and a moderate reduction in spike height. Even a small reduction of the resting potential resulted in typical changes of the spike responses characterized by a pronounced reduction in amplitude and increase in duration as the gradient was lowered until a minimal gradient was reached below which no spike was generated. The response patterns in normal and depolarized fibers were correlated to the slow active subthreshold processes occurring in muscle fibers during stimulation with linearly rising currents.
  • B Frankenhacuscr
  • A L Hodgkin
Frankenhacuscr, B., and Hodgkin, A. L., 1957, J. Phy~ot., 137, 217.