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 was suggested that KATP channels regulate Ca2+ homeostasis during β-adrenergic stress and that this is crucial for regulation of physical endurance . A shortening of cardiac action membrane potential is known to be associated with decreased Ca2+ influx and prevention of Ca2+ loading. Therefore, it was possible that Ca2+ homeostasis during stress could be improved in cardiac cells expressing more SUR2A. To test this hypothesis, we have measured intracellular Ca2+ levels in cardiac cells from the wild-type and SUR2A mice; a build up of Ca2+ over protracted time period would suggest a strained Ca2+ homeostasis. Thus, we have used isoprenaline (500 nM) and monitored Ca2+ levels in both cellular phenotypes. In cells from wild-type, there was a slow build up of intracellular Ca2+ during stimulation with isoprenaline (Fig. 6) and the average increase in Fluo-3 fluorescence under these conditions was 40.4 ± 2.3% (n = 12). In contrast, in SUR2A cells isoprenaline did not increase intracellular concentration at all (the average changes in intracellular Ca2+ concentration over 40 min. was –3.4 ± 2.3%, n = 8). The difference between wild-type and SUR2A mice was statistically significant (P < 0.01).
Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.