AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 279: H1849-H1857, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 4, H1849-H1857, October 2000

Mitochondrial NAD(P)H, ADP, oxidative phosphorylation, and contraction in isolated heart cells

Roy L. White1 and Beatrice A. Wittenberg2

1 Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140; and 2 Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461

To examine the relationship between mitochondrial NADH (NADHm) and cardiac work output, NADHm and the amplitude and frequency of the contractile response of electrically paced rat heart cells were measured at 25°C. With 5.4 mM glucose plus 2 mM beta -hydroxybutyrate, NADHm was reversibly decreased by 23%, and the amplitude of contraction was reversibly decreased by 27% during 4-Hz pacing. With glucose plus 2 mM pyruvate or with 10 mM 2-deoxy-D-glucose, NADHm was maintained during rapid pacing, and the contractile amplitude remained high. Phosphocreatine levels decreased with 2-deoxy-D-glucose administration but not with rapid pacing. Respiration increased to meet the increased ATP demand at 30°C. The data suggest that 1) when NADHm is decreased during rapid pacing with defined substrates, the amplitude of contraction is decreased; 2) the amplitude of contraction during electrical pacing does not change with rate of pacing when both the ATP and NADHm levels are continuously replenished; and 3) the replenishment of NADHm during pacing with physiological substrates may be rate-limited by substrate supply to mitochondrial dehydrogenases. During activation of mitochondrial dehydrogenases, or a significant increase in free ADP induced by 2-deoxy-D-glucose, this rate limitation is bypassed or overcome.

restwork transition; steady-state adenosine 5'-triphosphate utilization; substrate supply; phosphocreatine; lactate; 2-deoxy-D-glucose; reduced nicotinamide adenine dinucleotide; reduced nicotinamide adenine dinucleotide phosphate


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