Functional changes of vascular responses in familial hemiplegic migraine type 1

Abstract

The R192Q mutation of the CACNA1A gene, encoding for the α1 subunit of voltage‐gated P/Q‐type Ca2+ channels (Ca(v)2.1), is associated with familial hemiplegic migraine‐1. We aimed to investigate functional responses in different arteries of R192Q mutant mice. Since the phenotype is stronger in female R192Q mutants we isolated basilar, carotid artery and aorta of female mice. Using a wire myograph vasomotor responses to KCl, endothelin‐1 (ET‐1) and U46619 (a tromboxane A2 agonist) in basilar artery were evaluated. In aorta and carotid artery, vasoconstrictions to KCl, serotonin (5‐HT) and phenylephrine (PE) and vasodilatations to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. U46619‐induced constrictions slightly but not significantly increased in basilar artery of R192Q mice, but no changes were measured to KCl and ET‐1 induced constrictions. PE‐induced vasoconstriction decreased in both aorta and carotid artery of mutant mice. Vasomotor responses to 5‐HT decreased in carotid artery of R192Q knockin mice but it did not differ in aorta. No difference between groups to Ach and SNP vasodilations were observed. Our results indicate a change in vascular responsiveness to vasoconstrictors in carotid and aorta but not in basilar artery of R192Q mutant mice. Since basilar artery of mice does not have PE and 5‐HT constrictions, molecular studies are needed to test the changes in cerebral arteries.