Ion-channel regulation by G proteins

Ion channels are end-targets (effectors) ina large number of regulatory pathways that are initiated by G-protein-coupled neurotransmitters and hormones. Modulation of ion channels by G proteins can be indirect (via second messengers and protein kinases)or direct, via physical interactions between G-protein subunits and the channel protein. These direct physical interactions are the focus of this review. A direct regulation has been firmly established for several voltage-dependent Ca²⁺ channels and the G-protein-activated K⁺ channels. In these ion-channel families, the G-protein βγ subunits (Gβγ) are the active regulators, whereas the role of the α subunits (Gα) remains poorly understood. Accumulating evidence suggests that intricate relationships between the receptor, Gα, Gβγ and the ion channel play a major role in determining the specificity and magnitude of the overall regulation.