Interactions of cadmium and nickel with k channels of vascular smooth muscle

Previous studies have shown that environmentally significant concentrations (<1 μM) of large divalent cations increased vascular tone in resistance arteries. Because K channels are important regulators of vasoactivity, we studied the interactions of Cd and Ni on K channels of smooth muscle from bovine mesenteric artery using the planar bilayer method. We describe one type of small, Ca-insensitive K channel (K_s), and two types of large, Ca-activated K channels ([BK(Ca)], K_c1 and K_c2, that were identical with respect to single-channel conductance and K/Cl selectivity, but differed in Ca/voltage sensitivity. Neither metal affected the open probability (p_o) of K_s but both Cd and Ni, in concentrations greater than or equal to 100 nM, similarly decreased p_o of K_c1 and K_c2 from the intracellular side of the channel in the presence of 1 μM Ca. The effects of both Cd and Ni were reversed by 0.1 mM Ca. It is concluded that Cd and Ni, in concentrations less than 1 μM, can interact with the Ca/voltage sensor and inhibit BK(Ca) channels of vascular smooth muscle. These effects may partially explain the vascular tension induced by large divalent cations.