Electrophysiology of lead intoxication: effects on voltage-sensitive ion channels

Neuronal function depends on the activity of a variety of voltage-sensitive, ion-specific membrane channels, including channels permeable chiefly to sodium, potassium, and calcium. The plasma membranes of many neurons contain several types of each class of channel. In general, heavy metal ions exert little effect on voltage-sensitive sodium or potassium channels, but inhibit ion flow through voltage-sensitive calcium channels (VSCC). The literature abounds with descriptions of different types of calcium channels in vertebrate neurons. These descriptions suggest that there are many physiologically and pharmacologically distinct calcium channels, some of them possibly cell-type specific. Among the heavy metals, Pb2+ is one of the most potent inhibitors of VSCC in both vertebrate and invertebrate neurons. Some heavy metals, including Ni2+ and Cd2+, are fairly selective against certain types of calcium channels. Limited evidence suggests that Pb2+ inhibits all calcium channel types within a given cell, with only minor differences in potency. However, there appear to be substantial differences among cell types in the concentration dependence of calcium channel inhibition by Pb2+. Therefore, to appreciate the range of effects of Pb2+ on calcium channels throughout the nervous system, it will be important to examine a large number of cell types. Pb2+ is highly permeable through at least some types of VSCC. Entry of Pb2+ into the neuronal cytoplasm through VSCC, followed by disturbance of intracellular functions, may be a major mechanism of Pb2+ neurotoxicity.