The interaction between GPCR and Na+ channels via Go proteins in excitable cells

Our findings in excitable cells support the recent work of Kim et al. ( Exp Mol Med 57:2717–2728, 2025), which describes a direct interaction between ion channels and G proteins. We identified a direct interaction between muscarinic receptors, voltage-dependent sodium channels (VDSC), and G o proteins in mammalian excitable cells. Their interaction was dependent on the opening of the VDSC pore, and it implicated modifications in the VDSC transmembrane S6 segments that orchestrate the channel pore opening in coordination with the VDSC voltage sensors.