Kohlhardt M, Haap K, Figulla H R
Pflugers Arch. 1976 Oct 15;366(1):31-8. doi: 10.1007/BF02486557.
In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a "Wenckebach-like" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged.
在猫的离体乳头肌中，研究了细胞外pH从7.4降至5.5后钙内向电流和等长收缩力的变化。通过以下方式分析钙电流：(a)测量钙介导动作电位的上升速度；(b)在电压钳实验中使用双蔗糖间隙技术。1. 在pH为5.5时，钙介导动作电位的上升速度降至对照值的65%，而超射和动作电位持续时间几乎保持不变。此外，相对不应期延长，在某些情况下会出现“文氏现象”。在电压钳实验中，慢内向电流减少至初始对照值的50 - 60%，并且在很宽的电压范围内，电流 - 电压关系曲线向较弱电流方向移动。酸中毒不影响稳态失活，但改变了慢内向电流失活的动力学，并导致失活时间常数（tauinactivation）和恢复时间常数（taurecovery）增加。这表明酸中毒对慢膜通道产生复杂的影响。2. 细胞外pH降低并未改变钙电流对细胞外钙浓度变化（0.5 - 4 mM）或添加β刺激化合物异丙肾上腺素（2 mg/l）的正常反应。3. 在酸性介质中，等长收缩力在25分钟内降至对照值的40%，因此其反应比钙电流更强烈。这表明本实验中使用的酸中毒形式并非仅通过抑制钙电流产生其负性肌力作用。相反，必须假定存在额外的细胞内效应，最终导致收缩系统活性降低。4. 在pH 5.5时，过量的钙（4 mM）引起的收缩系统定量反应与正常pH时相同。相比之下，2 mg/l异丙肾上腺素的正性肌力作用更明显，而钙内向电流对这种β刺激化合物的敏感性保持不变。
