How do G proteins directly control neuronal [Ca.sup.2+] channel function?

[Ca.sup.2+] entry into neuronal cells is modulated by the activation of numerous G-protein-coupled receptors (GPCRs). Much effort has been invested in studying direct G-protein-mediated inhibition of voltage-dependent [Ca.sub.v]2 [Ca.sup.2+]. channels. This inhibition occurs through a series of convergent modifications in the biophysical properties of the channels. An integrated view of the structural organization of the G[beta][gamma]-dimer binding-site pocket within the channel is emerging. In this review, we discuss how variable geometry of the G[beta][gamma] binding pocket can yield distinct sets of channel inhibition. In addition, we propose specific mechanisms for the regulation of the channel by G proteins that take into account the regulatory input of each G[beta][gamma] binding element.