Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system

• Published in: Trends in neurosciences (Regular ed.) Vol. 15; no. 9; p. 351
• Main Authors: Llinás, R, Sugimori, M, Hillman, D E, Cherksey, B
• Format: Journal Article
• Language: English
• Published: England 01.09.1992
• Subjects: Animals; Calcium Channels - physiology; Central Nervous System - physiology; Electrophysiology; Humans
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/0166-2236(92)90053-b

In addition to the three types of voltage-dependent calcium channels presently recognized in the CNS, the L-, the T- and the N-types, a fourth distinct type known as the P-type channel has recently been described. This channel, initially recognized in Purkinje cells (and thus the name), is not blocked by dihydropyridines or by omega-conotoxin (GVIA), but is blocked by native funnel-web spider venom and by a polyamine (FTX) extracted from such venom. In addition, a synthetic polyamine (sFTX) has been produced that also specifically blocks P-channels in brain slices and at the neuromuscular junction, and blocks presynaptic Ca2+ currents in other vertebrate and invertebrate forms, as well as channels expressed in Xenopus oocytes following CNS mRNA injections. Using sFTX to form an affinity gel, a protein was isolated and reconstituted into lipid bilayers where it manifests single-channel properties that are electrophysiologically and pharmacologically similar to those of the native P-channels. Rabbits immunized with the isolated protein produced a polyclonal antibody that gave a positive western blot with the purified P-channel protein and generated a reaction product at specific sites in the CNS that agree with the physiological distribution of P-channel activity.