DIVALENT-CATIONS ACTIVATE SMALL-CONDUCTANCE (SK) AND LARGE-CONDUCTANCE (BK) CHANNELS IN MOUSE NEUROBLASTOMA-CELLS - SELECTIVE ACTIVATION OF SK CHANNELS BY CADMIUM

Effects of Cd2+, Co2+, Fe2+ and Mg2+ (1 muM and 100 muM) and Pb2+ (1 muM and 90 muM) 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+ almost-equal-to Pb2+ > Ca2+ > Co2+ much greater than 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+ much greater than 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.