Differential pharmacology of the cardiac anionic background current IAB

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 α-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, α-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.