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- Title
NADH supplementation decreases pinacidil-primed Ι<sub>K(ATP)</sub> in ventricular cardiomyocytes by increasing intracellular ATP.
- Authors
Pelzmann, Brigitte; Hallstrom, Seth; Schaffer, Peter; Lang, Petra; Nadlinger, Karl; Birkmayer, George D.; Vrecko, Caroline; Reibnegger, Gilbert; Koidl, Bernd
- Abstract
1 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 1K(ATP) was used as an indicator of subsarco-lemmal ATP concentration and intracellular adenine nucleotide contents were measured. 2 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. 3 Under physiological conditions (4.3 mM ATP in the pipette solution, ATP,) 1{subK(ATP)] did not contribute to basal electrical activity. 4 The ATP-dependent potassium (K(ATP) channel opener pinacidil activated 1K(ATP) dependent on [ATP], showing a significantly more pronounced activation at lower (1 mM) [ATP]. 5 Supplementation of cardiomyocytes with 300/μgml NADH (4-6h) resulted in a significantly reduced 1K(ATP) activation by pinacidil compared to control cells. The current density was 13.±3.78 (n= 6) versus 28.9± 3.38 pA pF (n= 19; P < 0.05).6 Equimolar amounts of the related compounds nicotinamide and NAD did not achieve a similar effect like NADH. 7 Measurement of adenine nucleotides by HPLC revealed a significant increase in intracellular ATP (NADH supplementation: 45.6±1.88 nmolmg1 protein versus control: 35.4±2.57 nmol mg protein. P < 0.000005), 8 These data show that supplementation of guinea-pig ventricular cardiomyocytes with NADH results in a decreased activation of 1K(ATP) by pinacidil compared to control myocytes, indicating a higher subsarcolemmal ATP concentration. 9 Analysis of intracellular adenine nucleotides by HPLC confirmed the significant increase in ATP.
- Publication
British Journal of Pharmacology, 2003, Vol 139, Issue 4, p749
- ISSN
0007-1188
- Publication type
Academic Journal
- DOI
10.1038/sj.bjp.0705300