Role of Calpastatin in Calcium Channel Regulation

Activity of Ca2+ channels in various tissues decreases when the cytoplasmic side of the channels is perfused with an artificial solution. This phenomenon is called as ‘run-down’ or ’wash-out’ and is most pronounced in the internally dialyzed cells or in the patches excised from cells (for review, see Hagiwara and Byerly 1983; Marty and Neher 1983; Kostyuk 1984; Armstrong, 1988; Kameyama et al. 1990b). In the heart the dihydropyridine-sensitive (L-type) Ca2+ channel, but not the transient (T-type) Ca2+ channel, shows run-down during the whole-cell recording and the single-channel recording in cell-free patches. (Cavalie et al, 1983; Nilius et al, 1985). Thus, the run-down may be closely related to mechanisms by which the channel activity is maintained or regulated. So far, several mechanisms have been suggested to underlie the run-down of Ca2+ channels: 1) dephosphorylation of a protein related to the Ca2+ channel (Doroshenko et al. 1984; Armstrong and Eckert 1987). 2) Ca2+-dependent inactivation of the channel (Byerly and Hagiwara 1982). 3) proteolysis of the channel protein by Ca2+-activated protease (Chad and Eckert 1985). 4) loss of cytoplasmic factor(s), such as ATP or GTP, that might be required for the channel activity (Schneider and Sperelakis 1974; Irisawa and Kokubun 1983; Ohya et al. 1987; Yatani et al. 1987).