Role of Voltage-Dependent and Ca2+-Activated K+ Channels on the Regulation of Isometric Force in Porcine Coronary Artery

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Abstract
We investigated the role of K+ channels in the regulation of vascular tone in de-endothelialized porcine coronary artery. Isometric force and intracellular Ca2+ ([Ca2+]i) under resting conditions were increased by treatment with 4-aminopyridine (4-AP, 1 mM), an inhibitor of voltage-dependent K+ (Kv) channels, but not by tetraethylammonium chloride (TEA, 1 mM) or charybdotoxin (100 nM), both inhibitors of Ca2+-activated K+ (KCa) channels, or glibenclamide (10 μM), an inhibitor of ATP-sensitive K+ channels. Under stimulated conditions with 9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F2α (U46619), 4-AP as well as TEA or charybdotoxin increased isometric force and [Ca2+]i, but not glibenclamide. 4-AP was the most potent in terms of depolarization of membrane potential compared with TEA or glibenclamide 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 oscillations. The force oscillations induced by 4-AP were inhibited by diltiazem (10 μM), an inhibitor of voltage-dependent Ca2+ channels, or TEA (1 mM), but not by glibenclamide (10 μM). These force oscillations may be associated with the periodic activation of KCa channels. These findings suggested that 4-AP-sensitive Kv channels play an important role in the control of vascular tone in both resting and stimulated conditions. Moreover, under stimulated conditions, KCa channels also have an important role in the regulation of vascular tone. Dysfunction of these channels induces abnormal vasoconstriction and may be implicated in vascular diseases such as hypertension and vasospasm.