Low external pH limits cell death of energy-depleted cardiomyocytes by attenuation of Ca2+ overload.

Low external pH limits cell death of energy-depleted cardiomyocytes by attenuation of Ca 2+ overload. Am. J. Physiol. 270 (Heart Circ. Physiol. 39): H2149-H2156, 1996.-We studied the effect of external pH (pH e ) on cell injury, ATP content, and intracellular concentration of Ca 2+ ([Ca 2+ ] i ), Na + ([Na + ] i ), and H + (pH i ) during metabolic inhibition (NaCN + 2-deoxyglucose) in neonatal rat cardiomyocytes. Cell death during metabolic inhibition decreased at pH e <7.4, with almost no cell death at pH e 6.0. Lowering pH e resulted in only temporary ATP conservation. During metabolic inhibition at pH e 7.4, [Ca 2+ ] i rose from 86 ± 44 nM to 2.5 ± 0.4 μM, but at pH e 6.0, [Ca 2+ ] i rose to only 510 ± 215 nM. During metabolic inhibition at pH e 7.4, pH i decreased from 7.25 ± 0.06 to 6.82 ± 0.16, but at pH e 6.0, pH i decreased to 6.34 ± 0.17. During metabolic inhibition at pH e 7.4, [Na + ] i increased from 9.1 ± 0.86 to 26.1 ± 4.1 mM. At pH e 6.0, [Na + ] i rose more rapidly, to 27.3 ± 3.5 mM. At pH e <7.4, sarcolemmal Na + /Ca 2+ exchanger activity, involved in the development of Ca 2+ overload, was decreased, as assessed during Na + -free incubation. We conclude that low pH e protects cardiomyocytes during metabolic inhibition by limiting Ca 2+ overload via Na+/Ca 2+ exchanger inhibition.