NADH supplementation decreases pinacidil‐primed I K(ATP) in ventricular cardiomyocytes by increasing intracellular ATP

• Published in: British journal of pharmacology 2003-06, Vol.139 (4), p.749-754
• Main Authors: Pelzmann, Brigitte, Hallström, Seth, Schaffer, Peter, Lang, Petra, Nadlinger, Karl, Birkmayer, George D, Vrecko, Karoline, Reibnegger, Gilbert, Koidl, Bernd
• Format: Article
• Language: English
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705300

The aim of this study was to investigate the effect of nicotinamide‐adenine dinucleotide (NADH) supplementation on the metabolic condition of isolated guinea‐pig ventricular cardiomyocytes. The pinacidil‐primed ATP‐dependent potassium current I K(ATP) was used as an indicator of subsarcolemmal ATP concentration and intracellular adenine nucleotide contents were measured. Membrane currents were studied using the patch‐clamp technique in the whole‐cell recording mode at 36–37°C. Adenine nucleotides were determined by HPLC. Under physiological conditions (4.3 m M ATP in the pipette solution, ATP i ) I K(ATP) did not contribute to basal electrical activity. The ATP‐dependent potassium (K (ATP) ) channel opener pinacidil activated I K(ATP) dependent on [ATP] i showing a significantly more pronounced activation at lower (1 m M ) [ATP] i . Supplementation of cardiomyocytes with 300 μ g ml −1 NADH (4–6 h) resulted in a significantly reduced I K(ATP) activation by pinacidil compared to control cells. The current density was 13.8±3.78 ( n =6) versus 28.9±3.38 pA pF −1 ( n =19; P