Strategies for Investigating G-Protein Modulation of Voltage-Gated Ca²⁺ Channels

Abstract

G-protein-coupled receptor modulation of voltage-gated ion channels is a common means of fine-tuning the response of channels to changes in membrane potential. Such modulation impacts physiological processes such as synaptic transmission, and hence therapeutic strategies often directly or indirectly target these pathways. As an exemplar of channel modulation, we examine strategies for investigating G-protein modulation of Ca_V2.2 or N-type voltage-gated Ca²⁺ channels. We focus on biochemical and genetic tools for defining the molecular mechanisms underlying the various forms of Ca_V2.2 channel modulation initiated following ligand binding to G-protein-coupled receptors.