Role of BKCa channels in smooth muscle cells of mesenteric artery from type 1 diabetic rats

Abstract

High conductance calcium‐activated potassium channels (BKCa) play a very important role in the regulation of arterial vascular tone through the hyperpolarization of the cell membrane. Diverse studies in blood vessels from different vascular beds in animal models with type I and II diabetes mellitus (DM) as well as in patients with type II diabetes have shown a decrease in the BK channels functional response which is probably related with cardiovascular complications secondary to this pathology that is the main cause of mortality in these patients.ObjectiveTo explore the expression and role of the BKCa channels in the contractility of the Mesenteric artery of Type I diabetic rats induced with streptozotocin.MethodsWe conducted isometric tension experiments in mesenteric artery rings (>500) to evaluate the function of the BKCa channel when pharmacologically activated with NS1619, a specific activator drug for this channel, or inhibiting it with Iberotoxin (Ibtx) a toxin that specifically blocks these channels. And with the purpose of knowing if BKCa channels are expressed in these arterial beds we conducted inmunofluorescence studies.ResultsWe observerd a small but not significant response to both activator and inhibitor of the BKCa channels in both control and experimental groups. The inmunofluorescence images indicated that the alfa subunit (the pore subunit) and beta 1 (modulator of the BKCa channel activity) are mostly expressed intracelullarly in endothelial cells and in the smooth muscle of these vessels. This suggests that the lack of response to NS1619 and IBtx is due to the fact that the channel is intracelullar and therefore its participation in the determination of muscle tone of the mesenteric artery is not significant. In contrast, preliminary results of isometric tension in first‐order rat mesenteric artery rings (approximately 400 μm in diameter), show a great participation of the BKCa channels in the regulation of the arterial tone of these vessels, by diminishing in about 80% the tension originated when contracting said rings with phenylephrine.ConclusionsBased on these results, we can conclude at present that the BKCa channels have a greater participation in the maintenance of muscle tone of small arteries (resistance) but not in big arteries (conductive) and that the type I diabetes does not affect the BKCa function in large conduncance arteries.Support or Funding InformationSupported by Conacyt 223350 to RETThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.