Solaro R J, Lee J A, Kentish J C, Allen D G
Department of Physiology, University College London, England.
Circ Res. 1988 Oct;63(4):779-87. doi: 10.1161/01.res.63.4.779.
We compared the response of ventricular muscle from adult and neonatal rats to hypercapnic acidosis. In adult muscle, acidosis caused an initial rapid fall of developed tension to 30 +/- 5% of control (mean +/- SEM, n = 6). However, tension recovered slowly to a steady state that was 56 +/- 6% of control. In neonatal muscle, acidosis caused a significantly smaller initial fall in tension to 43 +/- 3% (n = 8, p less than 0.05), but the tension then showed a subsequent slower fall to a steady state that was 29 +/- 4% of control, significantly less than in the adult (p less than 0.01). We have attempted to identify the mechanisms underlying these differences in response. In detergent-skinned myofibrils, reducing the pH from 7.0 to 6.5 caused a reduction in the pCa50 of 0.61 units in the adult muscle, but only 0.27 units in the neonatal ventricular muscle. Myofibrillar Ca2+ sensitivity in neonatal ventricular muscle is thus less susceptible to the effects of acidic pH than that of adult muscle. Since intracellular pH decreases rapidly on application of increased external CO2, these results are consistent with the finding that, initially, developed tension in neonatal muscles is less sensitive to the effects of acidosis. Sodium dodecylsulfate gel electrophoresis of myofibrillar preparations from adult and neonatal rats demonstrated differences in thin filament proteins, including troponin I, which may underlie the observed differences in Ca2+ sensitivity. In adult rat ventricular muscles, the slow recovery of tension during acidosis is associated with an increase in the amplitude of the Ca2+ transients to 263 +/- 34% of control (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
我们比较了成年大鼠和新生大鼠心室肌对高碳酸血症性酸中毒的反应。在成年肌中,酸中毒导致初始张力迅速下降至对照值的30±5%(平均值±标准误,n = 6)。然而,张力缓慢恢复至稳定状态,为对照值的56±6%。在新生肌中,酸中毒导致初始张力下降幅度显著较小,降至43±3%(n = 8,p<0.05),但随后张力下降更缓慢,至稳定状态时为对照值的29±4%,显著低于成年肌(p<0.01)。我们试图确定这些反应差异背后的机制。在去垢剂处理的肌原纤维中,将pH从7.0降至6.5导致成年肌中pCa50降低0.61个单位,而新生大鼠心室肌中仅降低0.27个单位。因此,新生大鼠心室肌的肌原纤维Ca2+敏感性比成年肌对酸性pH的影响更不敏感。由于增加外部CO2后细胞内pH迅速下降,这些结果与以下发现一致:最初,新生肌中的张力对酸中毒的影响不太敏感。成年和新生大鼠肌原纤维制剂的十二烷基硫酸钠凝胶电泳显示细肌丝蛋白存在差异,包括肌钙蛋白I,这可能是观察到的Ca2+敏感性差异的基础。在成年大鼠心室肌中,酸中毒期间张力的缓慢恢复与Ca2+瞬变幅度增加至对照值的263±34%有关(n = 4)。(摘要截断于250字)