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

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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Carmeliet E

doi

10.1016/S0006-3495(87)83315-5

subject

Has Abstract

pub_date

1987-01-01 00:00:00

pages

109-14

issue

1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(87)83315-5

journal_volume

51

pub_type

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