Large-conductance ion channel measured by whole-cell voltage clamp in single cardiac cells: modulation by beta-adrenergic stimulation and inhibition by octanol

Abstract

Membrane currents in single cardiac myocytes from adult guinea pigs were studied by means of the patch-clamp technique (whole-cell mode). During spontaneous or caffeine-induced Ca2+ release from the sarcoplasmic reticulum openings of a novel ion channel with large unitary conductance (280 pS) can be recorded. The density of these channels and/or its open-state probability are unusually low. On average in the whole-cell mode simultaneous maximum superposition of only four channels is observed. Opening events of this channel require an intracellular Ca2+ transient. Activation by [Ca2+]i, however, seems to be indirect; maximum opening activity occurs with a delay of several hundred milliseconds after peak [Ca2+]i. Single-channel activity can be enhanced by a cyclic AMP dependent process via beta-adrenergic stimulation of a cell. This can also be mimicked by caffeine, most likely via inhibition of phosphodiesterase. Octanol, an inhibitor of gap-junctional coupling in a variety of tissues, causes a concentration-dependent and reversible decrease in single-channel activity. Unitary conductance is not affected by octanol. The low density of these channels in cardiac membranes and their poor selectivity render any role in normal cardiac electrical activity unlikely. A possible relation of the channel to cardiac gap junctions is discussed.