Exercise training attenuates ageing-induced BK_Ca channel downregulation in rat coronary arteries

Physical inactivity and ageing are widely recognized as risk factors for development of coronary artery disease. One of the characteristic changes that occurs in aged coronary artery is downregulation of their large-conductance voltage- and calcium-activated K⁺ (BK_Ca) channels. In this study, we investigated the effects of moderate exercise training (ET) on the activity of BK_Ca channels in coronary arteries of aged rats. Old Fischer 344 rats (23-26 months old) were randomly assigned to sedentary (O-SED, n = 24) or exercise-trained groups (O-ET, n = 28). The O-ET rats underwent a progressive treadmill exercise-training programme for 60 min day^-1, 5 days week^-1 for 12 weeks. Young animals were used for comparison. Coronary arteries were mounted on a wire myograph, and contractions in response to 1, 10, 30, 50 and 100 nmol l^-1 iberiotoxin were compared. Iberiotoxin (100 nmol l^-1) contracted coronary arteries of young, O-SED and O-ET rats by 115 ± 14, 36 ± 5.6 and 61 ± 5% of 5-hydroxytryptamine-induced contractions, respectively. Patch-clamp studies revealed a larger magnitude of BK_Ca current in young (104 ± 15.6 pA pF^-1) compared with O-ET (44 ± 9 pA pF^-1) and least in O-SED coronary smooth muscle cells (8.6 ± 2 pA pF ^-1). Western immunoblotting was performed to study expression levels of BK_Ca channel proteins. The α and β1 subunits of the BK_Ca channel were reduced by 40 ± 3.5 and 30 ± 2.6%, respectively, in coronary arteries of old compared with young rats, and ET attenuated this reduction in expression level to 28 ± 2 and 12 ± 4%, respectively. Our results showed that ageing was associated with a reduction in BK_Ca channels, and ET partly reversed this reduction. We conclude that low-intensity ET may be beneficial in restoring age-related decline in coronary vasodilatory properties mediated by BK_Ca channels.