Interactions of monovalent cations with sodium channels in squid axon. I. Modification of physiological inactivation gating

G. S. Oxford, J. Z. Yeh

Research output: Contribution to journalArticle

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Abstract

Inactivation of Na channels has been studied in voltage-clamped, internally perfused squid giant axons during changes in the ionic composition of the intracellular solution. Peak Na currents are reduced when tetramethylammonium ions (TMA+) are substituted for Cs ions internally. The reduction reflects a rapid, voltage-dependent block of a site in the channel by TMA+. The estimated fractional electrical distance for the site is 10% of the channel length from the internal surface. Na tail currents are slowed by TMA+ and exhibit kinetics similar to those seen during certain drug treatments. Steady state I(Na) is simultaneously increased by TMA+, resulting in a 'cross-over' of current traces with those in Cs+ and in greatly diminished inactivation at positive membrane potentials. Despite the effect on steady state inactivation, the time constants for entry into and exit from the inactivated state are not significantly different in TMA+ and Cs+. Increasing intracellular Na also reduces steady state inactivation in a dose-dependent manner. Ratios of steady state I(Na) to peak I(Na) vary from ~0.14 in Cs+- or K+-perfused axons to ~0.4 in TMA+- or Na+ -perfused axons. These results are consistent with a scheme in which TMA+ or Na+ can interact with a binding site near the inner channel surface that may also be a binding or coordinating site for a natural inactivation particle. A simple competition between the ions and an inactivation particle is, however, not sufficient to account for the increase in steady state I(Na), and changes in the inactivation process itself must accompany the interaction of TMA+ and Na+ with the channel.

Original languageEnglish (US)
Pages (from-to)583-602
Number of pages20
JournalJournal of General Physiology
Volume85
Issue number4
StatePublished - 1985
Externally publishedYes

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Monovalent Cations
Decapodiformes
Sodium Channels
Axons
Ions
Membrane Potentials
Tail
Binding Sites
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Physiology

Cite this

Interactions of monovalent cations with sodium channels in squid axon. I. Modification of physiological inactivation gating. / Oxford, G. S.; Yeh, J. Z.

In: Journal of General Physiology, Vol. 85, No. 4, 1985, p. 583-602.

Research output: Contribution to journalArticle

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