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

Previous studies have shown that environmentally significant concentrations (< 1 microM) 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 (Ks), and two types of large, Ca-activated K channels ([BK(Ca)], Kc1 and Kc2, 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 (po) of Ks but both Cd and Ni, in concentrations greater than or equal to 100 nM, similarly decreased po of Kc1 and Kc2 from the intracellular side of the channel in the presence of 1 microM 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 microM, 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.