The role of cyclic AMP-dependent phosphorylation in the maintenance and modulation of voltage-activated calcium channels.

The predominant class of voltage-activated Ca channels in molluscan neurons (Helix) and a mammalian cell line (GH3) do not respond to membrane depolarization under conditions that prevent cAMP-dependent phosphorylation when the cytoplasm is replaced with standard physiological saline solutions. Under normal conditions, inactivation of these channels results from Ca ion entry and accumulation inside the cell. In dialyzed neurons, inactivation is enhanced in the presence of an exogenous Ca-dependent phosphatase, and inactivated channels appear to be susceptible to Ca-dependent proteolysis. Rephosphorylation of the channels by a cAMP-dependent kinase removes inactivation and protects the channels from proteolysis. Thus, phosphorylation/dephosphorylation reactions appear to be an important means of modulating Ca channel activity and may underlie both Ca-dependent inactivation and the metabolic maintenance of the channels.