Vanheel B, Van de Voorde J
Department of Physiology and Physiopathology, University of Gent, Belgium.
J Mol Cell Cardiol. 1995 Jul;27(7):1443-55. doi: 10.1006/jmcc.1995.0136.
The separate and the combined influence of lowering extracellular and intracellular pH on the extracellular accumulation of K+ ions in ischaemic mammalian cardiac tissue was investigated. Isolated guinea-pig papillary muscles were superfused in vitro while micro-electrode measurements of the transmembrane potentials and of the extracellular pH and K+ activity and of the intracellular pH and Na+ activity were performed. Muscles were reversibly subjected to spaced episodes of simulated ischaemia, and ischaemic K+ accumulation was measured. During normal superfusion, acidification of the intracellular pH (pHi approximately 6.8) effected by transient exposure to NH+4 containing superfusate was associated with an amiloride-sensitive rise of the intracellular Na+ activity (aiNa) from 5.1 +/- 0.5 to 19.5 +/- 2.4 mM. This increase was associated with a transient hyperpolarization of the membrane potential and shortening of the action potential duration from 190 +/- 7 to 111 +/- 16 ms. When a similar intracellular acidosis was induced 3 to 5 min before imposing ischaemia, extracellular K+ accumulation was increased compared to ischaemia alone. Surface K+ activity (asK) measured after 10 min of ischaemia was 9.6 +/- 0.8 mM following intracellular acidification v 6.4 +/- 0.4 mM following control superfusion. When the extracellular pH (pHo) was decreased to 6.85 prior to the ischaemic insult, extracellular K+ accumulation was not different from that observed during ischaemia after control superfusion (5.1 +/- 0.5 v 4.7 +/- 0.3 mM, respectively, after 10 min of ischaemia). When combined intracellular and extracellular acidosis was produced before ischaemia, the enhancing influence of lowered pHi on K+ accumulation was not observed. In these acid loading conditions, aiNa rose to the same level as observed following NH+4 withdrawal without simultaneous external acidification (26.9 +/- 2.0 mM v 23.9 +/- 2.0 mM, respectively). The results indicate that decreasing pHi before ischaemia accelerates the ischaemic increase of extracellular K+. On the other hand, although prior extracellular acidification by itself does not directly influence ischaemic K+ accumulation, it is in some way protective by reducing the intracellular proton-stimulated K+ efflux. This reduction seems not to be due to decreased cellular Na+ loading.
研究了降低细胞外和细胞内pH值对缺血哺乳动物心脏组织中K⁺离子细胞外蓄积的单独及联合影响。在体外对分离的豚鼠乳头肌进行灌流，同时用微电极测量跨膜电位、细胞外pH值和K⁺活性以及细胞内pH值和Na⁺活性。使肌肉可逆地经历间歇性模拟缺血，并测量缺血时K⁺的蓄积情况。在正常灌流期间，通过短暂暴露于含NH₄⁺的灌流液使细胞内pH值（pHi约为6.8）酸化，这与细胞内Na⁺活性（aiNa）从5.1±0.5 mM升至19.5±2.4 mM的氨氯地平敏感升高有关。这种升高与膜电位的短暂超极化以及动作电位持续时间从190±7 ms缩短至111±16 ms有关。当在缺血前3至5分钟诱导类似的细胞内酸中毒时，与单独缺血相比，细胞外K⁺蓄积增加。缺血10分钟后测量的表面K⁺活性（asK），细胞内酸化后为9.6±0.8 mM，而对照灌流后为6.4±0.4 mM。在缺血损伤前将细胞外pH值（pHo）降至6.85时，细胞外K⁺蓄积与对照灌流后缺血时观察到的情况无差异（缺血10分钟后分别为5.1±0.5 mM和4.7±0.3 mM）。当在缺血前产生细胞内和细胞外联合酸中毒时，未观察到降低的pHi对K⁺蓄积的增强影响。在这些酸负荷条件下，aiNa升至与NH₄⁺撤除后无同时外部酸化时观察到的相同水平（分别为26.9±2.0 mM和23.9±2.0 mM）。结果表明，缺血前降低pHi会加速细胞外K⁺的缺血性增加。另一方面，尽管预先的细胞外酸化本身并不直接影响缺血时K⁺的蓄积，但它通过减少细胞内质子刺激的K⁺外流在某种程度上具有保护作用。这种减少似乎不是由于细胞内Na⁺负荷降低所致。
