Aerobic exercise increases BK(Ca) channel contribution to regulation of mesenteric arterial tone by upregulating β1-subunit.

Substantial evidence has shown that exercise training produces numerous adaptations within the arteries. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) 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 BK(Ca) 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 BK(Ca) channels. Western immunoblotting was performed to study expression levels of BK(Ca) channel proteins. The maximal vascular contraction induced by noradrenaline (3 × 10(-5) M) was decreased after exercise training. Both TEA (3 × 10(-3) M) and iberiotoxin (3 × 10(-8) M) 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 Ca(2+) and voltage without altering the unitary conductance. The expression of BK(Ca) β1- but not α-subunit was significantly enhanced after exercise training. These data suggest that exercise training increases the contribution of the BK(Ca) channel to the regulation of vascular tone in mesenteric arteries, which is possibly mediated by upregulating β1-subunit protein to increase BK(Ca) channel activity.