Atsma D E, Bastiaanse E M, Van der Valk L, Van der Laarse A
Department of Cardiology, University Hospital, Leiden, The Netherlands.
Am J Physiol. 1996 Jun;270(6 Pt 2):H2149-56. doi: 10.1152/ajpheart.1996.270.6.H2149.
We studied the effect of external pH (pHe) on cell injury, ATP content, and intracellular concentration of Ca2+ ([Ca2+]i), Na+ ([Na+]i), and H+ (pHi) during metabolic inhibition (NaCN + 2-deoxyglucose) in neonatal rat cardiomyocytes. Cell death during metabolic inhibition decreased at pHe < 7.4, with almost no cell death at pHe 6.0. Lowering pHe resulted in only temporary ATP conservation. During metabolic inhibition at pHe 7.4, [Ca2+]i rose from 86 +/- 44 nM to 2.5 +/- 0.4 microM, but at pHe 6.0, [Ca2+]i rose to only 510 +/- 215 nM. During metabolic inhibition at pHe 7.4, pHi decreased from 7.25 +/- 0.06 to 6.82 +/- 0.16, but at pHe 6.0, pHi decreased to 6.34 +/- 0.17. During metabolic inhibition at pHe 7.4, [Na+]i increased from 9.1 +/- 0.86 to 26.1 +/- 4.1 mM. At pHe 6.0, [Na+]i rose more rapidly, to 27.3 +/- 3.5 mM. At pHe < 7.4, sarcolemmal Na+/Ca2+ exchanger activity, involved in the development of Ca2+ overload, was decreased, as assessed during Na(+)-free incubation. We conclude that low pHe protects cardiomyocytes during metabolic inhibition by limiting Ca2+ overload via Na+/Ca2+ exchanger inhibition.
我们研究了细胞外pH值（pHe）对新生大鼠心肌细胞代谢抑制（氰化钠+2-脱氧葡萄糖）过程中细胞损伤、ATP含量以及细胞内钙离子（[Ca2+]i）、钠离子（[Na+]i）和氢离子（pHi）浓度的影响。在代谢抑制期间，当pHe < 7.4时细胞死亡减少，在pHe 6.0时几乎没有细胞死亡。降低pHe仅导致ATP的暂时保存。在pHe 7.4进行代谢抑制时，[Ca2+]i从86±44 nM升至2.5±0.4 μM，但在pHe 6.0时，[Ca2+]i仅升至510±215 nM。在pHe 7.4进行代谢抑制时，pHi从7.25±0.06降至6.82±0.16，但在pHe 6.0时，pHi降至6.34±0.17。在pHe 7.4进行代谢抑制时，[Na+]i从9.1±0.86 mM增至26.1±4.1 mM。在pHe 6.0时，[Na+]i上升得更快，达到27.3±3.5 mM。在pHe < 7.4时，参与钙超载发展的肌膜钠/钙交换器活性降低，这是在无钠孵育期间评估得出的。我们得出结论，低pHe通过抑制钠/钙交换器限制钙超载，从而在代谢抑制期间保护心肌细胞。
