Diazepam, y-aminobutyric acid, and progesterone open K+ channels in myocytes from coronary arteries
Benzodiazepines enhance coronary blood flow and lower blood pressure, but the cellular basis of this action remains unclear. The present study now demonstrates a direct effect of diazepam, y-aminobutyric acid (GABA), and progesterone on the large conductance, Ca2+- and voltage-activated K+ channel (BK(Ca)) in single myocytes isolated from porcine coronary arteries. These GABA receptor agonists significantly increased whole-cell (perforated patch) K+ currents and stimulated the activity of single BK(Ca) channels in cell-attached patches dramatically. This effect is not mediated via cyclic AMP or cyclic GMP, but involves stimulation of Ca2+ influx in response to activation of a bicuculline-sensitive GABA(A)-like receptor. We propose that localized, subsarcolemmal increases in Ca2+ levels open BK(Ca) channels, thereby promoting K+ efflux, membrane repolarization, and coronary relaxation. This transduction pathway can now account, at least in part, for the direct vasodilatory effects of diazepam, progesterone, and GABA.
European journal of pharmacology
Jacob, Maryanne K. and White, Richard E., "Diazepam, y-aminobutyric acid, and progesterone open K+ channels in myocytes from coronary arteries" (2000). PCOM Scholarly Papers. 1101.