The voltage-gated calcium-channel β subunit: more than just an accessory

Voltage-gated Ca2+ channels (VGCCs) are involved in a number of excitatory processes in the cell that regulate muscle contraction, neurotransmitter release, gene regulation, and neuronal migration. They consist of a central pore-forming alpha(1) subunit together with a number of associated auxiliary subunits including a cytoplasmic beta subunit. With the aid of X-ray crystallography, it has been found that the beta subunits of VGCCs (beta(2a), beta(3), and beta(4)) interact strongly with the I-II loop of the pore-forming alpha(1) subunit. Here we discuss the potential interaction sites of beta(1a) with its alpha(1) subunit as well as the skeletal ryanodine receptor. We suggest that not only can beta(1a) interact with the alpha(1) subunit I-II loop, but more subtle interactions may be possible through the II-III loop via the beta(1a) SH3 domain. Such findings could have important implications with respect to EC coupling.