Kinetic mechanism of Na+ channel depression by taurine in guinea pig ventricular myocytes.
To examine effects of taurine on the kinetics of the Na+ channel current (I(Na)), action potentials and whole-cell Na+ currents were recorded from single ventricular myocytes of guinea pigs. Kinetic parameters for the activation and inactivation of I(Na) were determined in accordance with the first-order kinetic model. Changes in the kinetic parameters were assessed before and after taurine exposure (5-50 mM). While taurine at concentrations higher than 10 mM decreased the peak I(Na) by ca. 15%, the agent did not alter the reversal potential and the maximum Na+ conductance (GNa). Taurine shifted the steady-state inactivation (h(infinity)) curve toward the negative potential direction and decreased the slope of h(infinity). Concomitantly, the slope of the steady-state activation (m(infinity)) was also slightly decreased and the rate of inactivation in the large potential region (-40 to -30 mV) slightly increased, whereas the rate of the activation appeared to remain unchanged. It is suggested that taurine alters the surface charge of the membrane and reduces the number of charges moving upon activation and inactivation of channels, thereby reducing I(Na).
Sada
H
H
Department of Pharmacology, School of Medicine, Yamaguchi University, Ube, Japan.
Ban
T
T
Sperelakis
N
N
D000200:Action Potentials; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects*; D013654:Taurine / Q000494:pharmacology*; D016276:Ventricular Function
D015222:Sodium Channels; D013654:Taurine