Voltage-dependent block by tetrodotoxin of the sodium channel in rabbit cardiac Purkinje fibers

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Abstract

The two-microelectrode, voltage-clamp technique was applied to rabbit cardiac Purkinje fibers to study the interaction of tetrodotoxin (TTX) with the slowly inactivating Na current. Binding of TTX to rested, inactivated, and activated channels was estimated by measuring the relative decrease of current at the beginning (rested and inactivated channels) and the end (activated channels) of a 1 s depolarizing clamp to -45 mV. The accelerated decline of the Na current in the presence of a submaximal dose of TTX was interpreted as an increase in blocking efficiency upon depolarization. The experiments show that activated as well as inactivated channels are more sensitive to TTX than are rested channels. The dissociation equilibrium constants for the three states are 3.5 X 10(-6) M for the rested, 0.94 X 10(-6) M for the activated, and 0.75 X 10(-6) M for the inactivated channels. The time course of activation block was dependent on TTX concentration. Rate constants for association and dissociation of the activated state are 1.3 X 10(6) M-1 X s-1 and 1.5 s-1, respectively. © 1987, The Biophysical Society. All rights reserved.

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Carmeliet, E. (1987). Voltage-dependent block by tetrodotoxin of the sodium channel in rabbit cardiac Purkinje fibers. Biophysical Journal, 51(1), 109–114. https://doi.org/10.1016/S0006-3495(87)83315-5

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