Fig. 1.

Model depicting the G protein-mediated modulation of Ca²⁺ channels following mu opioid receptor (MOR) activation. The binding of the receptor agonist {i.e., [d-Ala2-N-Me-Phe4-Glycol5]-enkephalin (DAMGO)} leads to MOR activation and allosteric changes in the conformation of the heterotrimeric G protein. The Gα subunit releases GDP and binds GTP. The GTP-bound Gα thereafter dissociates from the Gβγ dimer, and the latter moiety binds to Ca²⁺ channels, leading to voltage-dependent inhibition of Ca²⁺ currents [N-type Ca2+ channel (Ca_V2.2)]. The cycle is completed following the hydrolysis of GTP and reassociation of the Gα and Gβγ subunits.