De. Atsma et al., LOW EXTERNAL PH LIMITS CELL-DEATH OF ENERGY-DEPLETED CARDIOMYOCYTES BY ATTENUATION OF CA2+ OVERLOAD, American journal of physiology. Heart and circulatory physiology, 39(6), 1996, pp. 2149-2156
We studied the effect of external pH (pH(e)) on cell injury, ATP conte
nt, and intracellular concentration of Ca2+ ([Ca2+](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. Lowe
ring pH(e) resulted in only temporary ATP conservation. During metabol
ic inhibition at pH(e) 7.4, [Ca2+](i) rose from 86 +/- 44 nM to 2.5 +/
- 0.4 mu M, but at pH(e) 6.0, [Ca2+](i) rose to only 510 +/- 215 nM. D
uring 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 fro
m 9.1 +/- 0.86 to 26.1 +/- 4.1 mM. At pH(e) 6.0, [Na+](i) rose more ra
pidly, to 27.3 +/- 3.5 mM. At pH(e) <7.4, sarcolemmal Na+/Ca2+ exchang
er activity, involved in the development of Ca2+ overload, was decreas
ed, as assessed during Na+-free incubation. We conclude that low pH(e)
protects cardiomyocytes during metabolic inhibition by limiting Ca2overload via Na+/Ca2+ exchanger inhibition.