ELECTROPHYSIOLOGY OF LEAD-INTOXICATION - EFFECTS ON VOLTAGE-SENSITIVEION CHANNELS

Neuronal function depends on the activity of a variety of voltage-sens itive, ion-specific membrane channels, including channels permeable ch iefly to sodium, potassium, and calcium. The plasma membranes of many neurons contain several types of each class of channel. In general, he avy metal ions exert little effect on voltage-sensitive sodium or pota ssium channels, but inhibit ion flow through voltage-sensitive calcium channels (VSCC). The literature abounds with descriptions of differen t types of calcium channels in vertebrate neurons. These descriptions suggest that there are many physiologically and pharmacologically dist inct calcium channels, some of them possibly cell-type specific. Among the heavy metals, Pb2+ is one of the most potent inhibitors of VSCC i n both vertebrate and invertebrate neurons. Some heavy metals, includi ng Ni2+ and Cd2+, are fairly selective against certain types of calciu m channels. Limited evidence suggests that Pb2+ inhibits all calcium c hannel types within a given cell, with only minor differences in poten cy. However, there appear to be substantial differences among cell typ es in the concentration dependence of calcium channel inhibition by Pb 2+ . Therefore, to appreciate the range of effects of Pb2+ on calcium channels throughout the nervous system, it will be important to examin e a large number of cell types. Pb2+ is highly permeable through at le ast some types of VSCC. Entry of Pb2+ into the neuronal cytoplasm thro ugh VSCC, followed by disturbance of intracellular functions, may be a major mechanism of Pb2+ neurotoxicity. (C) 1993 Intox Press, Inc.