Exercise Prevents Upregulation of RyRs–BK _Ca Coupling in Cerebral Arterial Smooth Muscle Cells From Spontaneously Hypertensive Rats

Abstract

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Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension: Therapeutic Implications

“…In a separate study, endurance exercise training was found to increase basal tone and the contribution of both BK Ca and K V channels to the regulation of tone in conduit coronary arteries [6], which is similar to another report showing increased BK Ca channels function in swine coronary smooth muscle cells after exercise [75]. A recent study from our laboratory [65] has confirmed that the upregulation of BK Ca β1 subunit in normotensive rats is the primary cause of the exerciseinduced increase of BK Ca channel currents and contribution to the vascular tone regulation, consistent with previous reports [62]. Furthermore, exercise training markedly increases the open probability (Po) and the mean open time, while simultaneously decreasing the mean closed time of BK Ca channels [66].…”

“…Other studies have suggested that chronic interval exercise training ameliorates the dysfunction of BK Ca channels in the coronary vasculature [56]. Our study [65] showed that the BK Ca β1 subunit and Ca 2+ release from RyRs (ryanodine receptors) increased in cerebral arteries of SHR, with an upregulation of RyRs-BK Ca coupling compared with normotensive rats, while endurance exercise markedly inhibited this increased coupling (Fig. 2).…”

“…Experiments in our laboratory have shown that K V 1.2 channel protein levels in SHR cerebral arteries and thoracic aortas are lower than that in WKY (data not shown). Although K V 1.5 channel expression in thoracic aorta was significantly lower in the SHR than in WKY, there was no significant difference in K V 1.5 channel protein expression in cerebral arteries between SHR and WKY [44,45,65]. Thus, the function and expression of K V channels proteins during hypertension may differ as a result of different experimental conditions and varied vascular beds, which alludes to the complex nature of K V channel function and expression in response to high blood pressure.…”

“…For example, Ca V 1.2 channels display higher current densities, activate at more negative potentials, display a slower inactivation, and recover at a faster rate from inactivation in the mesenteric arteries of spontaneously hypertensive rats (SHR) compared to Wistar Kyoto (WKY) rats [17]. A growing body of evidence confirms that both Ca V 1.2 channels protein expression and current densities are enhanced [10,65]. The upregulation of Ca V 1.2 channels during hypertension is connected with an increase in the pore-forming α1C subunit protein expression, and the underlying mechanisms may include changes in the α1C transcript levels and post-transcriptional modifications.…”

“…In SHR and renal hypertensive rats, loss of functional K V channels is associated with depolarization and elevated vascular tone in small cerebral arteries [71]. Exercise training increased the contribution of the K V channels to resting tone in SHR when compared to the sedentary group [44,45,65]. However, other studies have revealed that exercise does not resolve the lack of a reduction in the whole-cell K V current in exercise-trained hypercholesterolemic pigs [26], which means exercise training does not correct hypercholesterolemia-mediated attenuation of adenosine-induced vasodilation.…”