Calcium channel diversity: multiple roles of calcium channel subunits.

Until recently we held the simple view that voltage-gated calcium channels consisted of an alpha1 subunit, usually associated with auxiliary beta subunits and alpha(2)delta subunits and that skeletal muscle calcium channels were also associated with a gamma subunit. However, as discussed here, there is now evidence that the auxiliary subunits may also perform other roles unrelated to voltage-gated calcium entry. In the past students were taught the simplistic view that second messenger signaling to voltage-gated calcium channels involved mainly phosphorylation of L-type calcium channels, Ca(2+)-dependent inactivation via calmodulin, and direct G-protein-mediated inhibition of the neuronal N and P/Q channels. However, it is now clear that there are many other means of modulating calcium channel activity, including receptor-mediated internalization, proteolytic cleavage, phosphorylation of beta subunits, and interaction of calcium channels with other proteins, including enzymes masquerading as scaffold proteins.