Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart.
Bottom Line: We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A.The experiments focused on action membrane potential and intracellular Ca(2+) concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal K(ATP) channels and steady Ca(2+) levels in cardiomyocytes in response to β-adrenergic stimulation.The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.
Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.Show MeSH
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Mentions: It is generally accepted that the activation of β-adrenergic receptors and increased cardiac output and blood/oxygen supply underlies general adaptation to stress and ability of mammalians to sustain increased physical activity . The activation of KATP channels induces shortening of the action membrane potential. Therefore, we have assessed the duration of action membrane potential in cells from both phenotypes under control conditions and when stimulated with a β-adrenoceptor agonist, isoprenaline. Under control conditions, action membrane potential duration remained stable over time in both phenotypes, i.e. at the beginning of field stimulation duration of action membrane potential was 228 ± 11 msec. in wild-type and 223 ± 44 msec. in SUR2A mice (Fig. 4; n = 6–10; P = 0.90) and these values were not significantly changed after 30 min. of stimulation (action membrane potential duration; wild-type: 234 ± 17 msec., n = 10, P = 0.74; SUR2A: 218 ± 22 msec., n = 6, P = 0.89; Fig. 4). When isoprenaline (500 nM), an agonist of β-adrenergic receptors used to induce stress, was added, no changes in action membrane potential duration was observed in wild-type (from 243 ± 17 msec. in the absence to 254 ± 24 msec. in the presence of isoprenaline, n = 7, P = 0.61; Fig. 5). In contrast to the wild-type, in SUR2A mice action membrane potential was significantly shortened after exposure to 500 nM isoprenaline (from 240 ± 19 msec. in the absence to 163 ± 13 msec. in the presence of isoprenaline, n = 6, P = 0.0007; Fig. 5). To test whether this shortening is induced by the activation of sarcolemmal KATP channels, we have used glybenclamide, a blocker of KATP channels. When applied alone, glybenclamide (10 μM) did not alter duration of action membrane potential in SUR2A cells (data not shown), but glybenclamide (10 μM) blocked the shortening of action membrane potential in SUR2A cell (from 238 ± 15 msec. in the absence to 228 ± 37 msec. in the presence of isoprenaline and glybenclamide, n = 6, P = 0.76; Fig. 5).
Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.