Abstract
Ion channel remodeling is a dynamic process that occurs in response to various physiological and pathophysiological conditions including advanced age. One of the characteristic changes that occur in coronary arteries with ageing is down-regulation of calcium-activated potassium (KCa) channels. In this study, we investigated the effect of exercise training on age-induced down regulation of KCa channels in coronary vascular smooth muscle cells. Aged F344 (23–26 months old) rats underwent a progressive treadmill exercise training programfor 60min/day, 5 days/week for 12 weeks. Old unexercised age matched and young (12–16 weeks) rats were used as young and sedentary controls respectively. Coronary arteries were mounted on an isometric wire myograph to evaluate the functional role of KCa channels. Changes in resting tone in response to 10, 30, 50 and 100nM of iberiotoxin (IBX), a specific KCa channel blocker was normalized to maximum contraction in response to 5uM 5HT in each artery. 100 nM IBX increased resting tension in young, in old-sedentary and in old-exercised rats by 96%±5.8 (n=8), 29±5.7 (n=8) and 63±9.8 (n=9) respectively. Vascular smooth muscle cells were freshly-isolated from coronary arteries and families of whole-cell potassium currents were elicited by 10 mV depolarizing steps from a holding potential of −70 mV to +90 mV. IBX reduced potassium current maximally in sedentary young rats. However, potassium current reduction was more in old exercised than old sedentary rats. Our results indicate that in aged rats there is a reduction of KCa current and exercise training partially reversed this reduction. This may imply that low-intensity exercise training may be beneficial in restoring age-related decline in coronary vasodilatory properties.
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