Molecular basis for Ca2+ channel diversity.

Neurotransmitter release, neurosecretion, neuronal excitation, survival of neurons, and many other neuronal functions are controlled by the cellular calcium concentration. Calcium entry across the plasma membrane in response to membrane depolarization or activation of neurotransmitter receptors repre­ sents a major pathway for the cellular control of calcium. The voltage-depen­ dent calcium channels, activated and inactivated at a low or high membrane potential, are the best characterized plasmalemmal calcium entry pathway, primarily because powerful and specific channel blocking agents are available. The T (tiny)-type calcium channel is activated and inactivated at a low membrane potential and is present in a wide variety of excitable and non-excitable cells. T -type calcium channels are not considered in detail because the lack of specific blockers renders identification of cloned and expressed channels as T -type channels difficult. [n contrast, the high voltage activated and inactivated calcium channels have been subdivided into four distinct classes, using the organic calcium channel blockers (CaCB) (originally introduced by Fleckenstein and col­ leagues 1967) and several neurotoxins. They have been separated into the B (B stands for brain; B channels may include T-type channels)-, L (long lasting)-, N (neither L nor T channel)-, and P (Purkinje)-type calcium channels (Table I). B-, L-, Nand P-type calcium channels are activated at a high membrane potential (around -30 mY), inactivate slowly (long lasting), and are expressed in neuronal and non neuronal cells (Tsien et al 1991, Bertolini & Llinas 1992). Nand P-type calcium channels are blocked specifically by