K_Vα1 channels in murine arterioles: differential cellular expression and regulation of diameter

Abstract

The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K(+) channel (K(V)alpha1) subunits in precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells, whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. K(V)1.5 also localized specifically to arteriolar nerves in human pial membrane. K(V)1.5 was notable for its absence from smooth muscle cells. K(V)1.3, K(V)1.4, and K(V)1.6 were localized to endothelial and smooth muscle cells, although K(V)1.4 had a low expression level. K(V)1.1 was not expressed. Therefore, we show that different cell types of pial arterioles have distinct physiological expression profiles of K(V)alpha1, conferring the possibility of differential modulation by extracellular and second messengers. Furthermore, we show recombinant agitoxin-2 and margatoxin are potent vasoconstrictors, suggesting that K(V)alpha1 subunits have a major function in determining arteriolar resistance to blood flow.

Heterogeneous Kv1 function and expression in coronary myocytes from right and left ventricles in rats

“…antibody was able to detect protein of the predicted mass in mesenteric artery samples. Similar negative findings for Kv1.5 expression in vascular tissue have been reported and extensively discussed by Cheong et al (5). However, Li et al (22) recently observed Kv1.5 expression in left coronary myocytes.…”

The Mechanism of Endothelium-Independent Relaxation Induced by the Wine Polyphenol Resveratrol in Human Internal Mammary Artery

“…This reflects tissue differences in expression of K V 1 channels subtypes. In our study, margatoxin used in a concentration (10 nM) sufficient to block K V 1.1, K V 1.2, K V 1.3, and K V 1.6 channels abolished resveratrol-induced relaxation, suggesting that those channels might be included in the mechanism of resveratrol-induced endothelium-independent vasodilatation of HIMA (28,29). However, the fact that charybdotoxin, a potent blocker of K V 1.2 and K V 1.3 channels, did not reproduce the effect of margatoxin suggests that K V 1.1 and / or K V 1.6 channels may be the relevant target.…”

“…This peptide is a highly selective inhibitor of the K V 1 channels, especially 1.1, 1.2, 1.3, and 1.6 subtypes, but displays no affinity for the mammalian BK Ca channel (28,29). K V 1.2 and K V 1.3 channels were identified in vascular smooth muscle cell of rat mesenteric artery; K V 1.1 and K V 1.6 channels were detected in smooth muscle cells of rat aorta and rat pulmonary artery, but not in smooth muscle cells of mesenteric artery (30,31).…”

Selective Kv1.3 channel blocker as therapeutic for obesity and insulin resistance

“…First, Kv1.3 is minimally expressed in normal blood vessels (45)(46)(47), and only after vascular injury does its expression increase in proliferating vascular smooth muscle cells (48)(49)(50). Second, K v channel blockers would cause vasoconstriction, not vasodilation (51). Third, ShK-186 does not alter heart rate parameters or blood pressure in chronically treated rats (20), indicating that vascular changes, if any, are not sufficient to cause BAT-mediated thermogenesis.…”