Physiopathology of neuronal voltage-operated calcium channels

Voltage-operated calcium channels are multimeric transmembrane proteins crucially involved in control of calcium homeostasis. Multiple types of voltage-operated calcium channels have been described in both the nervous system and peripheral tissues. Different channels can be classified according to either their biophysical properties or their pharmacology, biochemical and molecular structure, and localization and functional role. Concentrating on neuronal cells, this paper reviews the different properties of low- and high-voltage activated channels, as well as various attempts to subdivide high-voltage activated channels into different subtypes (L, N, ?, P, etc.). The availability of selective drugs (such as dihydropyridines) and natural toxins (such as ?-Conotoxin, ?-agatoxin, and funnel-web spider toxins), which bind to specific channel subtypes, has greatly helped in channel classification. The emerging view is that there are many members of the family of voltage-operated calcium channels, each with its own molecular structure, a different pharmacology, a different localization, and possibly a different physiological role. Different calcium subtypes are selectively affected in human and animal diseases. The use of ?-Conotoxin has led to identification of the channel subtype (w) specifically affected in Lambert-Eaton myasthenic syndrome (a human disease of neurotransmission), and has permitted develop- ment of new diagnostic approaches to the disease.