Divalent cations activate small- (SK) and large-conductance (BK) channels in mouse neuroblastoma cells: selective activation of SK channels by cadmium

Abstract

Effects of Cd²⁺, Co²⁺, Fe²⁺ and Mg²⁺ (1 μM and 100 μM) and Pb²⁺ (1 μM and 90 μM) on single-channel properties of the small-conductance (SK) and large-conductance (BK) Ca²⁺-activated K⁺ channels were investigated in inside-out patches of N1E-115 mouse neuroblastoma cells. Cd²⁺, Co²⁺ and Pb²⁺, but not Fe²⁺ and Mg²⁺, cause SK channel opening. The potency of the metals in enhancing the SK channel-open probability follows the sequence Cd²⁺ ≈ Pb²⁺>Ca²⁺>Co²⁺≫ Mg²⁺, Fe²⁺. The four metals that cause SK channel opening are equipotent in enhancing the opening frequency of SK channels. The BK channel is activated by Pb²⁺ and Co²⁺, whereas Cd²⁺, Fe²⁺ and Mg²⁺ are ineffective. The potency of the metals in enhancing BK channel-open probability, open time and opening frequency follows the sequence Pb²⁺>Ca²⁺>Co²⁺≫Cd²⁺, Mg²⁺, Fe²⁺. The results show that SK channels are much more sensitive to Cd²⁺ than BK channels and indicate that Cd²⁺ is a selective agonist of SK channels. It is concluded that the various metal ions bind to the same regulatory site(s) at which Ca²⁺ activates the SK and BK channels under physiological conditions. The different potency sequences of metal ions with respect to BK and SK channel activation indicate that the regulatory sites of these Ca²⁺-activated K⁺ channeles have distinct chemical and physical properties.