Differential pharmacology of the cardiac anionic background current IAB

A novel anionic background conductance (IAB) 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 IAB 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 (ICl,vol), a cAMP-dependent Cl− current (ICl,cAMP)) IAB was augmented by tefluthrin, fenpropathrin, α-cypermethrin (but not tetramethrin). IAB was insensitive to chlorotoxin, gadolinium and picrotoxin. Thus, IAB exhibits a distinct pharmacological profile from other known cardiac anion conductances.