PMID: 9416735Jan 7, 1998Paper

Conformational state-dependent effects of halothane on cardiac Na+ current

Anesthesiology
H U WeigtW M Kwok

Abstract

The Na+ channel is voltage gated and characterized by three distinct states: closed, open, and inactivated. To identify the effects of halothane on the cardiac Na+ current (I(Na)) at various membrane potentials, the effects of 1.2 mM halothane at different holding potentials (V(H)) on I(Na) were examined in single, enzymatically isolated guinea pig ventricular myocytes. The I(Na) was recorded using the whole-cell configuration of the patch-clamp technique. Currents were generated from resting V(H)s of -110, -80, or -65 mV. State-dependent block was characterized by monitoring frequency dependence, tonic block, and removal of inactivation by veratridine. Halothane produced significant (P < 0.05) V(H)-dependent depressions of peak I(Na) (mean +/- SEM): 24.4 +/- 4.1% (V(H) = -110 mV), 42.1 +/- 3.4% (V(H) = -80 mV), and 75.2 +/- 1.5% (V(H) = -65 mV). Recovery from inactivation was significantly increased when cells were held at -80 mV (control, tau = 6.0 +/- 0.3 ms; halothane, tau = 7.1 +/- 0.4 ms), but not at -110 mV. When using a V(H) of -80 mV, halothane exhibited a use-dependent block, with block of I(Na) increasing from 8.6 +/- 1.4% to 30.7 +/- 3.5% at test pulse rates of 2 and 11 Hz, respectively. Use-dependent inhibition was...Continue Reading

References

Nov 1, 1991·Anesthesiology·J D Gallagher, C A McClernan
Feb 1, 1990·Anesthesiology·J L Atlee, Z J Bosnjak
Jan 1, 1986·The Japanese Journal of Physiology·Y IkemotoH Arimura
Jan 1, 1985·Annual Review of Medicine·H A Fozzard, J C Makielski
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Feb 1, 1997·Anesthesia and Analgesia·H U WeigtZ J Bosnjak

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Citations

Mar 18, 2003·Life Sciences·Alysia A ChavesCynthia A Carnes
Nov 11, 1999·British Journal of Pharmacology·J P MounseyJ R Moorman
Jun 23, 2007·Anesthesiology·Wei OuYang, Hugh C Hemmings
May 15, 2001·European Journal of Anaesthesiology·H C WartenbergB W Urban

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