SINGLE-CHANNEL AND FUNCTIONAL-CHARACTERISTICS OF A K-CA CHANNEL IN VASCULAR MUSCLE MEMBRANES OF HUMAN SAPHENOUS VEINS

The saphenous vein is used extensively to test for the effects of vaso dilator substances on venous reactivity, but the K+ channel types that mediate vasodilation have not been identified. Thus the goal of this study was to identify K+ channel types in vascular smooth muscle membr anes of human saphenous vein (HSV), which may contribute to membrane r epolarization and control of venous tone. Fourteen HSVs obtained from bypass surgery were enzymatically dissociated into single vascular myo cytes for patch-clamp analysis of inside-out patches (n = 81). HSV mem branes showed primarily high-conductance (226 pS) K+ channels, which a ccounted for greater than or equal to 95% of total patch current at ph ysiologic voltages. Channels were highly K+ selective, showed steep vo ltage and Ca2+ sensitivity, and were blocked by 100 nM iberiotoxin and less than or equal to 1 nM tetraethlyammonium (TEA). These Ca2+-sensi tive channels (K-Ca) also showed stacked openings in depolarized patch es exposed to 300-1,000 nM calcium, suggesting multiple functional K-C a channels ina single membrane patch. In tension-recording studies, is olated segments of HSV exposed to 100 nM norepinephrine contracted fur ther during progressive block of K-Ca channels by 0.1-3 mM TEA, sugges ting that K-Ca channels are pathways for repolarization and vasodilati on in HSV smooth muscle cells. Our finding of K-Ca channels in smooth muscle membranes of HSV, if extended to the plasma membranes of other human peripheral veins, suggests that this channel may represent a the rapeutic site for alleviation of conditions of increased venous tone.