Role of BKCa Channels in Mesenteric Artery Vascular Smooth Muscle Tone of Diabetic Rats

Abstract

High conductance calcium‐dependent potassium (BKCa) channels are broadly distributed in different tissues where their activity is regulated by depolarization and calcium. The BKCa channels are abundant in vascular smooth muscle and their role regulating contractile tone has been widely discussed. Several studies have reported that in diabetes mellitus (DM) potassium currents mediated by these channels are diminished, especially in those located in small resistant vessels. BKCa channels are present in conducting arteries as well but their role in muscle tone seems to be small if any.The objective of this work was to study the role of BKCa channels in muscle tone of diabetic rat mesenteric arteries.Male Wistar rats (190 ± 10 gr in weight) were used and DM was induced by injecting streptozotocin (65 mg/kg) into de caudal artery. At 4, 8 and 10 weeks after streptozotocin or vehicle injection, rats were sacrificed and the mesenteric artery excised. We conducted isometric tension experiments using 10 micromolar of the selective channel activator NS1619 or 100 nM Iberiotoxin, a specific blocker of the BKCa channels applied at the peak of the maximum contraction induced by 10 microM phenylephrine (PE). We also took confocal fluorescence images to identify the localization of the alpha subunit ‐BKCa channel in mesenteric artery rings.Tension experiments show that NS1619 had no significant effect on the contraction induced by PE neither in control or DM rats, no matter the time of DM evolution (for example, at 10 weeks the percentage of relaxation was of 11.93 ± 4.73 in DM and of 9.0 in control group). Similarly, Iberiotoxin by itself had a weak contractile effect on the vascular tone of control and DM groups (for example, DM of 10 weeks the percentage of contraction was of 2.65 ± 1.89 and of 6.07 ± 3.34 in control rats). Immunofluorescence shows that BKCa alpha subunit channel is present within the endothelium, the smooth muscle cells and the adventitia. However, it is noteworthy that the alpha subunit is more abundant in endothelial cells and to a lesser extent in muscle cells where it can be seen mainly at the cytoplasm.We concluded that in spite that the BKCa channels are expressed in mesenteric artery smooth muscle, they do not participate in maintaining the muscle tone because they are present mainly intracellulary. At present we are conducting experiments to know the localization of the BKCa beta subunit and see if DM affect it.Support or Funding InformationSupported by CONACYT Grant 223350 to RETThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.