Role of voltage-dependent and Ca2+-activated K+ channels on the regulationof isometric force in porcine coronary artery

We investigated the role of K+ channels in the regulation of vascular tone in de-endothelialized porcine coronary artery. Isometric force and intracel lular Ca2+ ([Ca2+](i)) under resting conditions were increased by treatment with 4-aminopyridine (4-AP, 1 mM), an inhibitor of voltage-dependent K+ (K -v) channels, but not by tetraethylammonium chloride (TEA, 1 mM) or charybd otoxin (100 nM), both inhibitors of Ca2+-activated K+(K-Ca) channels, or gl ibenclamide (10 mu M), an inhibitor of ATP-sensitive K+ channels. Under sti mulated conditions with 9,11-dideoxy-11 alpha,9 alpha-epoxymethano-prostagl andin F-2 alpha (U46619), 4-AP as well as TEA or charybdotoxin increased is ometric force and [Ca2+](i), but not glibenclamide. 4-AP was the most poten t in terms of depolarization of membrane potential compared with TEA or gli benclamide in the presence or absence of EGTA. In the presence of U46619, a high concentration of 4-AP (10 mM) caused a further contraction with oscil lations. The force oscillations induced by 4-AP were inhibited by diltiazem (10 mu M), an inhibitor of voltage-dependent Ca2+ channels, or TEA (1 mM), but not by glibenclamide (10 mu M). These force oscillations may be associ ated with the periodic activation of K-Ca channels. These findings suggeste d that 4-AP-sensitive K-v channels play an important role in the control of vascular tone in both resting and stimulated conditions. Moreover, under s timulated conditions, K-Ca channels also have an important role in the regu lation of vascular tone. Dysfunction of these channels induces abnormal vas oconstriction and may be implicated in vascular diseases such as hypertensi on and vasospasm. Copyright (C) 2000 S. Karger AG, Basel.