Functional roles of γ 2 , γ 3 and γ 4 , three new Ca 2+ channel subunits, in P/Q‐type Ca 2+ channel expressed in Xenopus oocytes

1 Stargazin or γ 2 , the product of the gene mutated in the stargazer mouse, is a homologue of the γ 1 protein, an accessory subunit of the skeletal muscle L‐type Ca 2+ channel. γ 2 is selectively expressed in the brain, and considered to be a putative neuronal Ca 2+ channel subunit based mainly on homology to γ 1 . Two new members of the γ family expressed in the brain have recently been identified: γ 3 and γ 4 . 2 We have co‐expressed, in Xenopus oocytes, the human γ 2, γ 3 and γ 4 subunits with the P/Q‐type (Ca V 2.1) Ca 2+ channel and different regulatory subunits (α 2 ‐δ; β 1 , β 2 , β 3 or β 4 ). 3 Subcellular distribution of the γ subunits confirmed their membrane localization. 4 Ba 2+ 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 Ba 2+ current. Expression of both β and γ subunits increased the appearance of the slow‐inactivating current. 5 Our data support a role for the γ subunit as a brain Ca 2+ 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.