Ca Channel b3 Subunit Enhances Voltage-Dependent Relief of G-Protein Inhibition Induced by Muscarinic Receptor Activation and Gbg

The Ca channel b subunit has been shown to reduce the magnitude of G-protein inhibition of Ca channels. However, neither the specificity of this action to different forms of G-protein inhibition nor the mechanism underlying this reduction in response is known. We have reported previously that coexpression of the Ca channel b3 subunit causes M2 muscarinic receptor-mediated inhibition of a1B Ca 21 currents to become more voltage-dependent. We report here that the b3 subunit increases the rate of relief of inhibition produced by a depolarizing prepulse and also shifts the voltage dependency of this relief to more hyperpolarized voltages; these effects are likely to be responsible for the reduction of inhibitory response of a1B channels to G-protein-mediated inhibition seen after coexpression of the Ca channel b3 subunit. Additionally, the b3 subunit alters the rate and voltage dependency of relief of the inhibition produced by coexpressed Gb1g1, in a manner similar to the changes it produces in relief of M2 receptorinduced inhibition. We conclude that the Ca channel b3 subunit reduces the magnitude of G-protein inhibition of a1B Ca channels by enhancing the rate of dissociation of the G-protein bg subunit from the Ca channel a1B subunit.