Abstract

We examined the effects of G-protein β and γ subunit heterodimers on human α_1B (N-type) Ca channels expressed in HEK293 cells. All of the known β subunits (β1–β5) produced voltage-dependent inhibition of α_1B Ca channels, depending on the γ subunit found in the heterodimer. β1–β4 subunits inhibited Ca channels when paired with γ1–γ3. However, β5 subunits only produced inhibition when paired with γ2. In contrast, heterodimers between β5 subunits and RGS (regulators of G-protein signaling) proteins containing GGL domains did not produce inhibition of Ca channels. However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the ability of Gβ5/γ2 heterodimers to inhibit Ca channels. Because all of the G-protein β subunits are found in the nervous system, we conclude that they may all potentially participate in Ca channel inhibition. The interaction of GGL-containing RGS proteins with Gβ5γ2 suggests a novel way in which Ca channels can be regulated.