Novel kinetics in the sodium conductance system predicted by the aggregation model of channel gating

Baumann, Gilbert

doi:10.1016/s0006-3495(81)84821-7

Cited by 10 publications

(4 citation statements)

References 10 publications

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“…This predicts that latency to Na+ channel opening, and therefore the decay rate of INa, might be different after brief depolarizations or after rapid pulse trains when channels might accumulate in this putative state and if this state is near the open state. Such a mechanism may account for the more rapid decay found in the INa traces after brief depolarizations (e.g., Frankenhaeuser, 1963;Baumann, 1981) in nerve or for the traces at the end of a rapid pulse train as compared with the first pulse in heart (Makielski and Falleroni, 1991).…”

Section: Discussionmentioning

confidence: 99%

Post-repolarization block of cardiac sodium channels by saxitoxin

Makielski

Satin

Fan

1993

Biophysical Journal

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Phasic block of rat cardiac Na+ current by saxitoxin was assessed using pulse trains and two-pulse voltage clamp protocols, and the results were fit to several kinetic models. For brief depolarizations (5 to 50 ms) the depolarization duration did not affect the rate of development or the amplitude of phasic block for pulse trains. The pulse train data were well described by a recurrence relation based upon the guarded receptor model, and it provided rate constants that accurately predicted first-pulse block as well as recovery time constants in response to two-pulse protocols. However, the amplitudes and rates of phasic block development at rapid rates (> 5 Hz) were less than the model predicted. For two pulse protocols with a short (10 ms) conditioning step to -30 mV, block developed only after repolarization to -150 mV and then recovered as the interpulse interval was increased. This suggested that phasic block under these conditions was caused by binding with increased affinity to a state that exists transiently after repolarization to -150 mV. This "post-repolarization block" was fit to a three-state model consisting of a transient state with high affinity for the toxin, the toxin bound state, and the ultimate resting state of the channel. This model accounted for the biphasic post-repolarization block development and recovery observed in two-pulse protocols, and it more accurately described phasic block in pulse trains. The transient state after repolarization was predicted to have a dwell time of 570 ms, an on rate for saxitoxin of 16 s-1 micro M-1, and an off rate of 0.2 s-1 (KD = 12 nM). These results and the proposed model suggest a novel variation on phasic block mechanisms and suggest a long-lived transient Na+ channel conformation during recovery.

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Section: Discussionmentioning

confidence: 99%

Post-repolarization block of cardiac sodium channels by saxitoxin

Makielski

Satin

Fan

1993

Biophysical Journal

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“…A possible answer to the first question is that the models tested in the Appendix were primarily designed to reproduce the time development of membrane conductance (c.f. Hodgkin-Huxley, 1952;and Baumann, 1981). Those kinetic schemes may fail when pressed beyond that original purpose.…”

Section: Discussionmentioning

confidence: 99%

“…Kinetic equations of gating models that contain mathematical features not found in the Hodgkin-Huxley equations were also integrated in dynamic steady states and the simulated gating currents subjected to harmonic analyses. These models included aggregation gating (Baumann, 1981) and an excited state model (Jakobsson, 1978). The aggregation kinetic equations contain nonlinear terms (i.e., products of dependent variables of the form x,x;) and the excited state model contains one rate constant whose value depends on the rate of change of the membrane potential.…”

Section: Other Kinetic Modelsmentioning

confidence: 99%

Gating current harmonics. I. Sodium channel activation gating in dynamic steady states

Fohlmeister¹,

Adelman²

1985

Biophysical Journal

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Internally perfused and pronase-treated giant axons were prepared for gating current measurements. Gating current records were obtained under large-amplitude sinusoidal voltage clamp after allowing for settling times into dynamic steady states. The current records were analyzed as functions of the mean membrane potential of the test sinusoid for which the amplitude and frequency were held constant. The nonlinear analysis consisted of determining the harmonic content (amplitudes and phases) of the distorted periodic current records. The most pronounced feature found in the analysis is a dominant second harmonic centered at Emean = +10 mV. A number of other characteristic harmonic behaviors were also observed. The harmonics tend to die away for very small (less than -60 mV) and very large (greater than +72 mV) values of Emean. The harmonic behavior seen in the axonal data is basically different from that seen in gating current simulations generated by the sodium-activation kinetics of standard models, including the Hodgkin-Huxley model. Some of the differences can be reconciled without requiring fundamental changes in the model kinetic schemes. However, the dominant harmonic feature seen in the axonal data cannot be reconciled with the model kinetics without a fundamental change in the models. The axonal data suggest two moving molecular components with independent degrees of freedom whose properties are outlined on the basis of the data presented herein.

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“…Initial condition-induced changes have been reported for the time constant of the macroscopic inactivation by Chandler and Meves (1970) and for the time course of the tail currents by Goldman and Hahin (1978) and by Sigworth (1981). The change of the time constants with the initial conditions can be explained either by the aggregation model of Baumann (1981Baumann ( , 1983, or by assuming that the calculated time constants are the mean of two or more time constants, whose weight changes with the initial conditions (see Goldman & Hahin, 1978 Sigworth (1981). He showed that in the node of Ranvier channels which open late during a depolarization stay open longer.…”

Section: R~ci~-mentioning

confidence: 99%

Evidence for multiple open states of sodium channels in neuroblastoma cells

Nagy

1987

J. Membrain Biol.

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Open times of voltage-gated sodium channels in neuroblastoma cells were measured during repolarization (following a short depolarizing conditioning pulse) and during moderate depolarization. Conditional and unconditional channel open-time histograms were best fitted by the sum of two exponentials. (The conditional open time was measured from the end of the conditioning pulse until an open channel shuts provided it was open at t = 0). Time constants of both histograms depended on the post-pulse and were shifted to more positive potentials with increasing conditioning pulse potential. This shift could be explained by assuming more than two time constants in the histograms, which could not be separated. Channel open-time histograms from single-pulse experiments showed a maximum at t greater than 0. These histograms could be best fitted by an exponential function with three time constants. One term of this function included the difference of two exponentials resulting in a maximum at t greater than 0. Open-time histograms showed a definite time dependence. At 2 to 6.5 msec after the beginning of the depolarization the best fit could be obtained by the difference of two exponentials. To these components another term had to be added at 0 to 2 msec. Between 6.5 and 14.0 msec the sum of two exponentials, and after 14.0 msec a single exponential resulted in a good fit. The results support the hypothesis that sodium channels in neuroblastoma cells may have multiple open states. Two of these states are irreversibly coupled.

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Novel kinetics in the sodium conductance system predicted by the aggregation model of channel gating

Cited by 10 publications

References 10 publications

Post-repolarization block of cardiac sodium channels by saxitoxin

Post-repolarization block of cardiac sodium channels by saxitoxin

Gating current harmonics. I. Sodium channel activation gating in dynamic steady states

Evidence for multiple open states of sodium channels in neuroblastoma cells

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