Aerobic exercise increases BKCa channel contribution to regulation of mesenteric arterial tone by upregulating β1-subunit

Abstract

New Findings: • What is the central question of this study? Calcium-activated K channels (BK) play critical roles in regulating cellular excitability and vascular tone. Exercise-training has beneficial effects on cardiovascular diseases which may result from an improvement of the vascular functions. However, the molecular targets and mechanisms underlying this action remain largely unknown in peripheral resistance arteries. This paper asks the question, do BK channels play a role in bringing about these changes? • What is the main finding and its importance? This investigation is the first to demonstrate that aerobic exercise training increases the contribution of BK channels to regulation of vascular tone in mesenteric arteries. We found that it is mediated by upregulation of the Beta-1 but not alpha1-subunit protein to increase BK channel activity. Substantial evidence has shown that exercise training produces numerous adaptations within the arteries. Large-conductance Ca2+-activated K+ (BKCa) channels are expressed broadly on smooth muscle cells and play an important role in the regulation of vascular tone. The present study was designed to investigate the mechanisms by which the BKCa channel underlies the exercise-induced improvement of the vascular function in mesenteric arteries. Male Wistar rats (180-200 g) were trained for 12 weeks on a treadmill (EX group) and compared with age-matched sedentary (SED) animals. Blood pressure and vascular contractility of mesenteric arteries were measured. Inside-out patch-clamp recording was applied on the freshly separated mesenteric smooth muscle cells to investigate the gating characteristics of BKCa channels. Western immunoblotting was performed to study expression levels of BKCa channel proteins. The maximal vascular contraction induced by noradrenaline (3 × 10-5m) was decreased after exercise training. Both TEA (3 × 10-3m) and iberiotoxin (3 × 10-8m) induced a significant increase of vessel tension in both SED and EX groups, but these effects were more pronounced in EX rats compared with SED animals. Inside-out patch-clamp recording showed that exercise training significantly increased the open probability, decreased the mean closed time and increased the mean open time and the sensitivity to Ca2+ and voltage without altering the unitary conductance. The expression of BKCaβ1- but not α-subunit was significantly enhanced after exercise training. These data suggest that exercise training increases the contribution of the BKCa channel to the regulation of vascular tone in mesenteric arteries, which is possibly mediated by upregulating β1-subunit protein to increase BKCa channel activity. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.