Role of Voltage-Dependent and Ca ²⁺-Activated K ⁺ Channels on the Regulation of Isometric Force in Porcine Coronary Artery

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 m M), an inhibitor of voltage-dependent K⁺ (K_v) channels, but not by tetraethylammonium chloride (TEA, 1 m M) or charybdotoxin (100 n M), both inhibitors of Ca²⁺-activated K⁺ (K_Ca) channels, or glibenclamide (10 μ M), an inhibitor of ATP-sensitive K⁺ channels. Under stimulated conditions with 9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F_2α (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 m M) caused a further contraction with oscillations. The force oscillations induced by 4-AP were inhibited by diltiazem (10 μ M), an inhibitor of voltage-dependent Ca²⁺ channels, or TEA (1 m M), but not by glibenclamide (10 μ M). These force oscillations may be associated with the periodic activation of K_Ca channels. These findings suggested 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 stimulated conditions, K_Ca 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.