Yano T, Hotokebuchi N, Morioka T, Nishi K
Department of Pharmacology, Kumamoto University Medical School, Japan.
Am J Physiol. 1989 Sep;257(3 Pt 2):H996-1004. doi: 10.1152/ajpheart.1989.257.3.H996.
We examined the relationship among intracellular sodium activity (aiNa), intracellular pH (pHi), and delayed afterdepolarization (DAD) in guinea pig ventricular papillary muscle fibers exposed to K-free solution in vitro, using Na+- and H+-selective microelectrodes. In unstimulated papillary muscles, exposure to K-free solution caused a rapid increase in aiNa of 16.2-22 mM at the end of a 20-min superfusion period with rates of 0.51-0.73 mM/min. This was paralleled by a decrease in intracellular pH of 0.10-0.15 units. DADs were induced after a train of driven action potentials 5-15 min after superfusion with K-free solution at the elevated aiNa from the steady-state level. Prevention of intracellular acidosis associated with the increased aiNa in K-free solution by external alkalosis at pH 8.0 enhanced the amplitude of the DAD, whereas restoration of external pH to 7.4 and a further acidification of external pH to 6.4 suppressed DADs. We concluded that intracellular acidosis associated with the increased aiNa per se increased the likelihood for inhibition of sarcoplasmic reticulum Ca2+ release in spite of increased cytosolic Ca2+.
我们使用钠和氢选择性微电极，在体外无钾溶液中对豚鼠心室乳头肌纤维进行研究，以检测细胞内钠活性（aiNa）、细胞内pH（pHi）和延迟后去极化（DAD）之间的关系。在未受刺激的乳头肌中，在无钾溶液中持续灌注20分钟结束时，暴露于无钾溶液会使aiNa迅速增加16.2 - 22 mM，速率为0.51 - 0.73 mM/分钟。同时细胞内pH会下降0.10 - 0.15个单位。在无钾溶液灌注后5 - 15分钟，当aiNa从稳态水平升高时，一串驱动动作电位后会诱发DAD。在pH 8.0时通过外部碱化防止与无钾溶液中aiNa增加相关的细胞内酸中毒，会增强DAD的幅度，而将外部pH恢复到7.4以及进一步将外部pH酸化至6.4会抑制DAD。我们得出结论，尽管细胞溶质钙增加，但与aiNa增加本身相关的细胞内酸中毒会增加抑制肌浆网Ca2+释放的可能性。
