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Protective Effect of HOE642, a Selective Blocker of Na + ‐H + Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes
Author(s) -
RuizMeana Marisol,
GarciaDorado David,
Juliá Margarita,
Inserte Javier,
Siegmund Berthold,
Ladilov Yuri,
Piper Michael,
Tritto Francesco Paolo,
González Miguel A.,
SolerSoler J.
Publication year - 2000
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1111/j.1469-445x.2000.01908.x
Subject(s) - chemistry , cytosol , intracellular , sodium–hydrogen antiporter , biophysics , extracellular , sodium , perfusion , myocyte , membrane potential , medicine , endocrinology , pharmacology , biochemistry , biology , enzyme , organic chemistry
The objective of this study was to investigate the effect of Na + ‐H + exchange (NHE) and HCO 3 − ‐Na + symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re‐energization (Rx). The effects of perfusion of HCO 3 − or HCO 3 − ‐free buffer with or without the NHE inhibitor HOE642 (7 μM) were investigated during MI and Rx. In HCO 3 − ‐free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% ( P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx ( P < 0.01). The presence of HCO 3 − abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca 2+ (fura‐2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na + rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO 3 − ‐dependent transporters are inhibited. This effect is independent of changes in cytosolic Na + or Ca 2+ concentrations.