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Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury

2000; American Physical Society; Volume: 278; Issue: 5 Linguagem: Inglês

10.1152/ajpheart.2000.278.5.h1457

1522-1539

Claudia Schäfer, Yury Ladilov, Britta Siegmund, H. M. Piper,

Muscle metabolism and nutrition

Isolated cardiomyocytes from adult rats were incubated in anoxic bicarbonate-buffered media at extracellular pH (pH o ) 6.4 until a cytosolic Ca 2+ overload and intracellular pH (pH i ) of 6.4 were reached. On reoxygenation, the pH of the medium was changed to 7.4 to activate the Na + /H + exchanger (NHE) and the Na + -[Formula: see text] symporter (NBS). The reoxygenation was performed in the absence or presence of the NHE inhibitor HOE-642 (3 μmol/l) and/or the NBS inhibitor DIDS (0.5 mmol/l ), as in bicarbonate-free media. In reoxygenated control cells pH i rapidly recovered to the preanoxic level, and a burst of spontaneous oscillations of cytosolic Ca 2+ occurred, accompanied by the development of hypercontracture. When NBS and NHE were simultaneously inhibited during reoxygenation, pH i recovery was prevented, Ca 2+ oscillations were attenuated, and hypercontracture was abolished. Sole inhibition of NBS or NHE showed no protection against hypercontracture. In the absence of cytosolic acidosis, HOE-642 or DIDS did not prevent hypercontracture induced by Ca 2+ overload. The results demonstrate that simultaneous inhibition of NHE and NBS is needed to protect myocardial cells against reoxygenation-induced hypercontracture.