Differential modulation of cardiac and skeletal muscle ryanodine receptors by NADH

Abstract

The effects of nicotinamide‐adenine dinucleotides (NADH, NAD⁺, NADPH) on ryanodine receptor channels (RyRs) from cardiac and skeletal muscle were compared in planar bilayers. NADH decreased cardiac RyR activity, which was counteracted by NAD⁺. In contrast, NADH and NAD⁺ both activated skeletal RyRs. NADPH/NADP⁺ were without effect on cardiac and skeletal RyRs. In the presence of ATP, NADH inhibition of cardiac RyRs remained. Differently, in the presence of ATP both NADH and NAD⁺ were ineffective as skeletal RyR agonists, suggesting interactions with the ATP binding site(s) of the channels. The results suggest that the direct effect of cytosolic NADH is physiologically important for the modulation of cardiac RyRs.