Differential effects of heavy metal ions on Ca2+-dependent K+ channels
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1. The ability of various divalent metal ions to substitute for Ca2+ in activating distinct types of Ca2+-dependent K+ [K+(Ca2+] channels has been investigated in excised, inside-out membrane patches of human erthrocytes and of clonal N1E-115 mouse neuroblastoma cells using the patch clamp technique. The effects of the various metal ions have been compared and related to the effects of Ca2+.
2. At concentrations between 1 and 100 µM Pb2+, Cd2+ and Co2+ activate intermediate conductance K+(Ca2+) channels in erythrocytes and large conductance K+(Ca2+) channels in neuroblastoma cells. Pb2+ and Co2+, but not Cd2+, activate small conductance K+(Ca2+) channels in neuroblastoma cells. Mg2+ and Fe2+ do not activate any of the K+(Ca2+) channels.
3. Rank orders of the potencies for K+(Ca2+) activation are Pb2+, Cd2+>Ca2+, Co2+>>Mg2+, Fe2+ for the intermediate erythrocyte K+(Ca2+) channel, and Pb2+, Cd2+>Ca2+>Co2+>>Mg2+, Fe2+ for the small, and Pb2+>Ca2+>Co2+>>Cd2+, Mg2+, Fe2+ for the large K+(Ca2+) channel in neuroblastoma cells.
4. At high concentrations Pb2+, Cd2+, and Co2+ block K+(Ca2+) channels in erythrocytes by reducing the opening frequency of the channels and by reducing the single channel amplitude. The potency orders of the two blocking effects are Pb2+>Cd2+, Co2+>>Ca2+, and Cd2+>Pb2+, Co2+>>Ca2+, respectively, and are distinct from the potency orders for activation.
5. It is concluded that the different subtypes of K+(Ca2+) channels contain distinct regulatory sites involved in metal ion binding and channel opening. The K+(Ca2+) channel in erythrocytes appears to contain additional metal ion interaction sites involved in channel block.
Key wordslead cadmium cobalt single channel patch clamp calcium-activated potassium channel human erythrocyte N1E-115 mouse neuroblastoma cell
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