Functional roles of γ2, γ3 and γ4, three new Ca2+ channel subunits, in P/Q‐type Ca2+ channel expressed in Xenopus oocytes

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Abstract
Stargazin or γ2, the product of the gene mutated in the stargazer mouse, is a homologue of the γ1 protein, an accessory subunit of the skeletal muscle L-type Ca2+ channel. γ2 is selectively expressed in the brain, and considered to be a putative neuronal Ca2+ channel subunit based mainly on homology to γ1. Two new members of the γ family expressed in the brain have recently been identified: γ3 and γ4. We have co-expressed, in Xenopus oocytes, the human γ2,γ3 and γ4 subunits with the P/Q-type (CaV2.1) Ca2+ channel and different regulatory subunits (α2-δ; β1, β2, β3 or β4). Subcellular distribution of the γ subunits confirmed their membrane localization. Ba2+ currents, recorded using two-electrode voltage clamp, showed that the effects of the γ subunits on the electrophysiological properties of the channel are, most of the time, minor. However, a fraction of the oocytes expressing β subunits displayed an unusual slow-inactivating Ba2+ current. Expression of both β and γ subunits increased the appearance of the slow-inactivating current. Our data support a role for the γ subunit as a brain Ca2+ channel modulatory subunit and suggest that β and γ subunits are involved in a switch between two regulatory modes of the P/Q-type channel inactivation.