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Background: The ATP-sensitive K⁺ (K_ATP) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involves opening of vascular or neuronal K_ATP channels and mast cell degranulation. Using rat as a model, we studied the molecular presence of K_ATP channels in the trigeminovascular system. Furthermore, we examined whether K_ATP channel openers stimulate the in vitro release of CGRP and whether they degranulate dural mast cells.

Methods: mRNA and protein expression of K_ATP channel subunits were studied in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) by qPCR and western blotting. In vitro CGRP release was studied after application of levcromakalim (1 µM) and …