The link between sodium activation and inactivation

Peganov, É. M.; Timin, E. N.; Bi, Khodorov

doi:10.1007/bf00803287

Cited by 5 publications

(6 citation statements)

References 5 publications

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“…Such delays in the development of inactivation were first reported by Armstrong (1970) in Dosidicus axons, and have also been seen in the node (Peganov, 1973). In Myxicola, the delay is reduced if a larger conditioning pulse, with a more rapidly rising gNa, is used (Goldman and Schauf, 1972), and this result has also been confirmed in the node (Peganov, 1973). Chandler et al (1965) first suggested that delays in the development of inactivation might be expected if activation and inactivation are coupled, owing to the time taken for the development of the gNa during the conditioning pulse.…”

Section: Introductionsupporting

confidence: 68%

“…In Myxicola (Goldman and Schauf, 1972) there is an initial delay in the development of the inactivation of the gNa, and also in the recovery from inactivation (Schauf, 1974). Such delays in the development of inactivation were first reported by Armstrong (1970) in Dosidicus axons, and have also been seen in the node (Peganov, 1973). In Myxicola, the delay is reduced if a larger conditioning pulse, with a more rapidly rising gNa, is used (Goldman and Schauf, 1972), and this result has also been confirmed in the node (Peganov, 1973).…”

Section: Introductionmentioning

confidence: 69%

“…A view of the sodium gating machinery which is consistent with the observed behavior of the gNa, is to imagine that the gate, in Myxicola, is composed of five independent subunits, each of the type illustrated in scheme I. The proposal of coupled activationinactivation kinetics for the gNa, first made by Hodgkin and Huxley (1952 c) has been considered by a number of other investigators (Mullins, 1959;Hoyt, 1963;Goldman, 1964;Chandler and Meves, 1970;Moore and Jakobsson, 1971;Peganov et al, 1973;Tredgold, 1973). More recently Bezanilla and Armstrong (1974) have interpreted some of their observations on sodium gating currents in terms of a coupled activationinactivation process.…”

Section: Discussionmentioning

confidence: 92%

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Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable

Goldman¹

1975

Biophysical Journal

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A variety of experimental observations in Myxicola and other preparations indicate that the sodium conductance, gNa, has properties quite different from those described by the m and h variables of Hodgkin and Huxley. A new quantitative description of the gNa is presented in which the gNa is assumed to be proportional to the fifth power of a generalized second-order variable, i.e., gNa = g'Na times v to the fifth, v = -Kav + K2U = K3, U = K4U + K5v + K6. This model is shown to be able to quantitatively simulate all of the experimentally observed behavior of the gNa. A view of the sodium gate consistent with these kinetics is to imagine it to be composed of five independent subunits, each of the type A eq. B eq. C eq. A where A represents the resting state, B the conducting state, and C the inactivated state. A model in which the subunit is of the type A eq. B eq. C could not simulate the experimental observations. It was concluded that two processes are sufficient to account for all of the behavior of the gNa.

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Section: Introductionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 92%

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Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable

Goldman¹

1975

Biophysical Journal

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“…Voltage-clamp studies of Myxicola axons (Goldman and Schauf, 1973;Schauf, 1973), lobster axons (Oxford and Pooler, 1975), and frog nerve (Peganov, et al, 1974) have demonstrated that sodium inactivation time constants measured from the decay of sodium current during a maintained depolarization are substantially smaller than the inactivation time constants determined at the same membrane potential using conditioning prepulses. Such data is difficult to reconcile with the existence of independent gating processes for sodium activation and inactivation.…”

Section: Introductionmentioning

confidence: 99%

Further studies of activation-inactivation coupling in Myxicola axons. Insensitivity to changes in calcium concentration

Schauf¹,

Davis²

1975

Biophysical Journal

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In Myxicola axons subjected to moderate depolarizations the sodium inactivation time constants obtained from the decay of sodium current during a maintained depolarizatin (TSh) are substantially smaller than inactivation time constants determined at the same potential from the effect of changes in the duration of conditioning prepulses (Tph). This report extends these observations to positive membrane potentials and demonstrates that for sufficiently large depolarizations TSh and Tph become comparable. The ratio of inactivation time constants, Tph/TSh, is unaffected by changes in [Ca++] provided total divalent cation concentration is maintained constant, while changes in total divalent ion concentrations produce simple voltage shifts comparable to those obtained from measurement of membrane sodium or potassium conductances. Sodium inactivation delay was quantitatively determined as a function of membrane potential, and found to be similarly unaffected by changes in [Ca++] at constant total divalent ion concentration. Inactivation delay is, however, directly proportional to the activation rate constant over a wide range of potentials.

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“…In their mathematical model, sodium 'activation' and 'inactivation' are represented by two kinetically separate parameters, n3 and h respectively, each with a characteristic dependence on membrane potential and time. Other mathematical models have successfully described the transient nature of sodium permeability using coupled gating parameters (Hoyt, 1963;Peganov, Timin & Khodorov, 1973). The mechanisms underlying gating remain obscure, but probably involve charge movements in response to changes in the membrane potential (Hodgkin & Huxley, 1952d;Keynes & Rojas, 1973).…”

mentioning

confidence: 99%

Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom.

Cahalan¹

1975

The Journal of Physiology

187

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SUAMARY1. The effect of Centruroides sculpturatus scorpion venom on single frog myelinated nerve fibres was studied. Sodium currents through the nodal membrane were measured under voltage-clamp conditions before and after exposure to venom in Ringer solution 1-5 ,ug/ml. for 1-3 min.2. Centruroides venom brings about repetitive firing and increased membrane potential noise. Spontaneous firing was also observed. Eventually the nodal membrane becomes inexcitable following venom treatment.3. Under voltage clamp with a step depolarization of the membrane potential, activation and inactivation of sodium currents appear normal. However, upon repolarization a novel sodium current turns on, reaches a peak within about 25 msec, and then declines over several hundred milliseconds. As the amplitude and duration of the depolarizing pulse are increased, the size of the venom-induced current that follows also increases.4. The venom-induced current turns on exponentially with a time constant near the value of the time constant for recovery from inactivation, Th' at the resting membrane potential. A depolarizing pulse inactivates this new current component, while a hyperpolarizing pulse leads to a larger venom-induced current immediately after the hyperpolarization. Its time course and membrane potential dependence indicate that the venominduced current is modulated by the sodium inactivation process.5. The membrane potential dependence of sodium activation in some channels is shifted by 40-S50 mV in the hyperpolarizing direction. Depolarization increases the proportion of channels with shifted activation gating by first-order kinetics. Following a depolarizing pulse the activation * Present address: Deparment of Physiology, University of Rochester, Rochester, New York. M. D. CAHALAN parameter, i3, remains elevated for hundreds of milliseconds, allowing channels to reopen as recovery from inactivation occurs.6. A kinetic model with normal inactivation gating and shifted activation gating in some channels accounts for the observed voltage-clamp currents and for the repetitive firing evoked by Centruroides venom. In the model normal channels are converted to channels with shifted activation gating by a voltage dependent reaction.7. The results suggest limits to possible coupling between sodium channel activation and inactivation. Transitions of the inactivation parameter, h, can occur normally in channels with a shifted membrane potential dependence for activation.

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The link between sodium activation and inactivation

Cited by 5 publications

References 5 publications

Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable

Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable

Further studies of activation-inactivation coupling in Myxicola axons. Insensitivity to changes in calcium concentration

Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom.

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