Lead and zinc block a voltage-activated calcium channel of Aplysia neurons.
1. The effects of Pb2+ and Zn2+ on the peak of the voltage-activated calcium current of Aplysia neurons were examined. Calcium currents were reversibly blocked by Pb2+ at concentrations that did not significantly affect potassium and sodium currents and by Zn2+ at concentrations associated with a delay and reduction of peak sodium and potassium currents. 2. The block by both was concentration dependent, and percentage blockade was reduced in elevated Ca2+. The threshold Pb2+ concentration for blockade in 20 mM Ca artificial sea water (ASW) was approximately 1 microM, whereas for Zn2+ it was 2 mM. The Hill coefficient for Pb2+ action was near 1.0 under all conditions, whereas for Zn2+ it was 1.4-1.6. 3. With addition of Pb2+, the voltage at which peak calcium current was generated shifted to hyperpolarized voltages, an effect similar to that caused by reduction of Ca2+ concentration in the absence of Pb2+. Zn2+ shifted the voltage at which peak current was generated in a depolarizing direction. 4. Pb2+ did not significantly change inactivation but shifted the voltage dependence of activation to hyperpolarized voltages in a dose-dependent manner. Zn2+ shifted both activation and inactivation in a depolarizing direction in a dose-dependent fashion. 5. The blockade of calcium currents by Pb2+ but not Zn2+ was highly voltage dependent and increased with depolarization. 6. Our results suggest that Pb2+ is a specific, potent, competitive, and reversible blocker of calcium currents. These observations are consistent with a competition by Pb2+ with Ca2+ at a binding site within the calcium channel. In contrast, the blockade of calcium currents by Zn2+ is probably through actions at fixed charge sites external to the channel.
Büsselberg
D
D
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12237.
Evans
M L
ML
Rahmann
H
H
Carpenter
D O
DO
D000818:Animals; D001048:Aplysia; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007854:Lead / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D009994:Osmolar Concentration; D015032:Zinc / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007854:Lead; D015032:Zinc