Differential pharmacology of the cardiac anionic background current I(AB).

John J Borg, Jules C Hancox, Henggui Zhang, Christopher Ian Spencer, Hongyu Li, Roland Z Kozlowski

Index: Eur. J. Pharmacol. 569(3) , 163-70, (2007)

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Abstract

A novel anionic background conductance (I(AB)) in cardiac ventricular myocytes has recently been identified but at present there is comparatively little information on its pharmacological modulation. This study investigated the effects of on I(AB) of four pyrethroid agents tefluthrin (a selective activator of this current), tetramethrin, fenpropathrin and alpha-cypermethrin in addition to other well known chloride channel modulators (chlorotoxin, gadolinium and picrotoxin). Guinea-pig ventricular myocytes were isolated using an enzymatic and mechanical dispersion procedure and all electrophysiological measurements were made using the whole-cell patch-clamp technique. In contrast to other anion conductances (stretch- or volume-regulated chloride current (I(Cl,vol)), a cAMP-dependent Cl(-) current (I(Cl,cAMP))) I(AB) was augmented by tefluthrin, fenpropathrin, alpha-cypermethrin (but not tetramethrin). I(AB) was insensitive to chlorotoxin, gadolinium and picrotoxin. Thus, I(AB) exhibits a distinct pharmacological profile from other known cardiac anion conductances.