Mayoux E, Coutry N, Lechêne P, Marotte F, Hoffmann C, Ventura-Clapier R
Institut National de la Santé et de la Recherche Médicale, Université de Paris Sud, Châtenay-Malabry, France.
Am J Physiol. 1994 May;266(5 Pt 2):H2051-60. doi: 10.1152/ajpheart.1994.266.5.H2051.
Effects of alkalosis (pH 7.4) or acidosis (pH 6.8) on the intrinsic mechanical properties of control and pressure-overloaded rat hearts were studied in Triton X-100-treated left ventricular fiber bundles. In control bundles, Ca sensitivity [pCa required for one-half maximal response (pCa50)] was 5.520 +/- 0.012 at pH 7.1. Alkalosis increased it by 0.357 +/- 0.018 pCa unit, whereas acidosis decreased it by 0.365 +/- 0.014 pCa unit with no change in Hill coefficient. Maximal tension was decreased by acidic pH and increased by alkaline pH. Stiffness was measured by the response to quick length changes. Acidosis decreased maximal stiffness but increased the stiffness-to-force ratio, whereas alkalosis increased maximal stiffness but had no effect on stiffness-to-force ratio, suggesting that acidosis decreased the force generated per cross bridge. Alkalosis increased the time constant of tension recovery following a quick stretch from 10.6 +/- 0.66 to 17.45 +/- 1.83 ms, suggesting a decreased cross-bridge cycling rate. Pressure overload induced by thoracic aortic stenosis for 4-6 wk led to a 200% cardiac hypertrophy associated with a shift from fast to slow ventricular myosin. pCa50 of hypertrophied bundles was not different from control (5.541 +/- 0.012). Ca sensitivity was increased by 0.383 +/- 0.008 in alkaline medium and decreased by 0.325 +/- 0.009 in acidic medium. Stiffness-to-force ratio was decreased in acidic pH, and the time constant of tension recovery was increased from 31.0 +/- 0.4 to 34.9 +/- 0.25 ms by alkalosis. In hypertrophied bundles, maximal tension was decreased by acidic pH but not changed by alkalosis. These results show that in the small pH range of our study 1) pH changes have symmetrical effects on Ca sensitivity in both control and hypertrophied bundles, 2) a decrease or an increase in H+ concentration does not have symmetrical effects on the mechanics of the cross bridges, and 3) changes in the phenotype of contractile proteins induced by aortic stenosis do not influence Ca sensitivity, only moderately influence the response to pH changes, and mainly affect the cross-bridge cycling rate.
在经曲拉通X - 100处理的大鼠左心室纤维束中，研究了碱中毒（pH 7.4）或酸中毒（pH 6.8）对对照和压力超负荷大鼠心脏固有机械特性的影响。在对照纤维束中，pH 7.1时的钙敏感性[产生最大反应一半时所需的pCa（pCa50）]为5.520±0.012。碱中毒使其增加0.357±0.018个pCa单位，而酸中毒使其降低0.365±0.014个pCa单位，希尔系数无变化。酸性pH使最大张力降低，碱性pH使其增加。通过对快速长度变化的反应来测量刚度。酸中毒降低了最大刚度，但增加了刚度与力的比值，而碱中毒增加了最大刚度，但对刚度与力的比值无影响，这表明酸中毒降低了每个横桥产生的力。碱中毒使快速拉伸后张力恢复的时间常数从10.6±0.66毫秒增加到17.45±1.83毫秒，表明横桥循环速率降低。胸主动脉缩窄4 - 6周引起的压力超负荷导致心脏肥大200%，伴有从快速型心室肌球蛋白向慢速型的转变。肥大纤维束的pCa50与对照无差异（5.541±0.012）。在碱性介质中钙敏感性增加0.383±0.008，在酸性介质中降低0.325±0.009。酸性pH下刚度与力的比值降低，碱中毒使张力恢复的时间常数从31.0±0.4增加到34.9±0.25毫秒。在肥大纤维束中，酸性pH使最大张力降低，但碱中毒对其无影响。这些结果表明，在我们研究的小pH范围内：1）pH变化对对照和肥大纤维束中的钙敏感性有对称影响；2）H⁺浓度的降低或增加对横桥力学没有对称影响；3）主动脉缩窄诱导的收缩蛋白表型变化不影响钙敏感性，仅适度影响对pH变化的反应，且主要影响横桥循环速率。
