Studies on Voltage-Gated Calcium Channels by Means of Fluorescent [Ca2+]i Indicators

Most excitable cells respond to depolarization with a rapid increase of their Ca2+ permeability, due to the opening of voltage-gated Ca2+ channels (Ca2+ VOCS) in the plasma membrane (Hagiwara and Byerly 1981; Reuter 1984). Opening of these channels causes the cytosolic concentration of Ca2+, [Ca2+]i, to rise quickly, beginning in the cytosolic region(s) immediately adjacent to the plasma membrane. The [Ca2+]i rise is opposed by processes that expell Ca2+ from the cell (active pumping by a Ca2+ ATPase and Na+/Ca2+ exchange) or cause its segregation within intracellular, membrane-bounded campartments (a high affinity microsomal store as well as the mitochondria). Up to now, studies on Ca2+ VOCs were carried out primarily by electro-physiology (classical techniques as well as patch clamping) and by Ca2+ influx experiments. By the use of these techniques, a number of important achievements were obtained (Hagiwara and Byerly 1981; Reuter 1984), including the recent demonstration of the heterogeneous nature of Ca2+ VOCs. Following the simple nomenclature proposed by Nowicky et al. (1985), the various types of Ca2+ VOCs so far identified will be referred to here as the T (transient, or low-threshold) VOCs, probably involved in pacemaking; the L (long-lasting, or high-threshold), the classical Ca2+ VOCs that are affected by dehydropyridine drugs; and the N (neither transient, nor long-lasting) VOCs, present in neurons, that might be preferentially located in the presynaptic membrane (Nowicky et al. 1985).