Role of Ca2+-Activated K+ Channels on Adrenergic Responses of Human Saphenous Vein

Background We studied the participation of K+ channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca2+ channels on modulation of adrenergic responses by K+ channels blockade. Methods Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. Results Iberiotoxin (10−7 mol/L), an inhibitor of large conductance Ca2+-activated K+ channels, and charybdotoxin (10−7 mol/L), an inhibitor of both large and intermediate conductance Ca2+-activated K+ channels, enhanced the contractions elicited by electrical field stimulation and produced a leftward shift of the concentration–response curve to norepinephrine. In contrast, the inhibitor of small conductance Ca2+-activated K+ channels apamin (10−6 mol/L) did not modify the contractile response to electrical field stimulation or norepinephrine. In the presence of the dihydropyridine Ca2+-channel blocker nifedipine (10−6mol/L), iberiotoxin and charybdotoxin failed to enhance the contractile responses to electrical field stimulation and norepinephrine. Conclusions The results suggest that large conductance Ca2+-activated K+ channels are activated by stimulation with norepinephrine to counteract the adrenergic-induced contractions of human saphenous vein. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca2+ entry through L-type voltage-dependent Ca2+ channels.