Transfer of β subunit regulation from high to low voltage-gated Ca2+ channels

High voltage-activated Ca2+ channel expression and gating is controlled by their β subunits. Although the sites of interaction are known at the atomic level, how β modulates gating remains to be determined. Using a chimeric approach, β subunit regulation was conferred to a low voltage-activated channel. Regulation was dependent on a rigid linker connecting the α1 interaction domain to IS6. Chimeric channels also revealed a role for IS6 in channel gating. Taken together, these results support a direct coupling model where β subunits alter movements in IS6 that occur as the channel transits between closed, open, and inactivated states.