K-ARTERY VASCULAR SMOOTH-MUSCLE CELLS( CURRENTS IN HUMAN CORONARY)

K+ channels and their currents are important in vascular tone regulati on and are potential therapeutic targets; however, K+ channels in huma n coronary artery vascular smooth muscle cells (VSMCs) have received l ittle attention. We examined K+ currents in freshly isolated VSMCs fro m human coronary arteries (n=368 from 32 human hearts) with convention al patch-clamp or perforated-patch techniques with nystatin. We detect ed four different K+ currents: (1) the delayed rectifier K+ current, I -K(dr); (2) the Ca2+-activated K- current, I-K(Ca); (3) the nonrectify ing noninactivating outward ATP-dependent K+ current, I-K(ATP); and (4 ) the spontaneous transient outward K+ current, I-K(STOC). K+ channels underlying spontaneous transient outward currents probably represent a single clustered population of Ca2+-activated K+ channels functional ly associated with Ca2+ release channels in the sarcoplasmic reticulum . Inwardly rectifying K+ currents were not observed. K+ currents were unevenly distributed in that they were not uniformly exhibited by all cells. The most prominent K+ currents were I-K(Ca) (100%) and I-K(dr) (46%). I-K(STOC)s, which have not been previously described in humans, were present in 67% of VSMCs. I-K(ATP) was small under physiological conditions; however, I-K(ATP) increased markedly after cell stimulatio n with exogenous or endogenous coronary vasodilators. Thus, I-K(ATP) m ay be particularly relevant in ischemia and could be of special import ance as a therapeutic target. We conclude that human coronary VSMCs ha ve unique K+ currents that differ sufficiently from those of other spe cies, thus making the investigation of human material clinically relev ant. The findings suggest potential avenues for further therapeutic re search.