¿p#1 Background and Purpose: Calcitonin gene-related peptide (CGRP) is a potent, clinically relevant endogenous vasodilator, but the precise intracellular signalling pathways remain unclear, particularly in small coronary arteries. Experimental Approach: This study used ex vivo myography and intracellular recording techniques to investigate α-CGRP-induced vasorelaxation and vascular smooth muscle cell (VSMC) hyperpolarization in myogenically-active rat isolated coronary arteries. Key Results: CGRP-induced vasorelaxation was not dependent on the endothelium, but relied heavily on K + channel activation. Immunohistochemistry indicated Kv7 and BK Ca channel expression in VSMC and endothelial cells (ECs). A combination of the K V7 channel inhibitor, linopirdine, and the BK Ca channel inhibitor, paxilline, significantly attenuated CGRP-induced vasorelaxation in endothelium-intact or denuded arteries. Electrophysiology confirmed that CGRP induced hyperpolarization and showed this was prevented by linopirdine and paxilline, also demonstrating a role for K V7 and BK Ca channels in suppressing depolarizing smooth muscle spikes. These spikes were also suppressed by NO• and HNO donors, resulting in hyperpolarization. Gβγ subunit inhibition with gallein markedly right-shifted CGRP-induced vasorelaxation in both endothelium-intact and denuded coronary arteries. Conclusion and Implications: α-CGRP stimulates robust vasorelaxation in the coronary microvasculature that relies on Gβγ subunit activated VSMC hyperpolarization involving K V7 and BK Ca channels. These data enhance understanding of coronary microvascular physiology and inform the design of future therapeutic strategies targeting coronary vascular dysfunction.