Facilitation of Ca2+ current in excitable cells

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Abstract

Voltage-dependent Ca2+ channels are one of the main routes for the entry of Ca2+ into excitable cells. These channels are unique in cell-signalling terms in that they can transduce an electrical signal (membrane depolarization) via Ca2+ entry into a chemical signal, by virtue of the diverse range of intracellular Ca2+-dependent enzymes and processes. In a variety of cell types, currents through voltage-dependent Ca2+ channels can be increased in amplitude by a number of means. Although the term facilitation was originally defined as an increase of Ca2+ current resulting from one or a train of prepulses to depolarizing voltages, there is a great deal of overlap between facilitation by this means and enhancement by other routes, such as phosphorylation. Trends Neurosci. (1996) 19, 35–43

Section snippets

Facilitation by depolarizing voltage steps

An important means by which Ca2+ current was found to be reversibly enhanced (leading to the term ‘facilitation’[9]) was manipulation of the membrane potential. Facilitation by depolarizing prepulses was first identified in bovine chromaffin cells by Neher and colleagues[10](Fig. 2A–D), and has more recently been investigated in detail by Artalejo and Fox9, 12who observed large enhancements of Ca2+ current, often a doubling[12], compared with the smaller enhancement observed previously[10].

Voltage-dependence of G-protein-mediated effects

It is a well-known phenomenon in a number of neuronal and neurosecretory systems that activation of a pertussis-toxin-sensitive G protein causes inhibition of Ca2+ currents, which is manifested by a reduction in amplitude and usually a slowed activation of the currents (Fig. 3; for review, see Ref. [2]). In a number of cell types, this G protein has been identified as Go, either by reconstitution experiments[66], or by experiments using G-protein-specific antibodies to inhibit function67, 68or

Concluding remarks

Facilitation of Ca2+ current has been studied extensively in bovine chromaffin cells in an elegant series of papers by Artalejo and colleagues9, 12, 14, 79, 89. It is typified by a voltage- and phosphorylation-dependent enhancement of Ca2+ current that might be mimicked by cAMP-dependent phosphorylation and by DHP agonists. In other cell types, it has been found that subsets of the different forms of facilitation might occur in different permutations. For example, in cerebellar granule

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