Fox R M, Morgan R M, Markham A
School of Health Sciences, University of Sunderland, Tyne and Wear, U.K.
Biochem Pharmacol. 1993 May 25;45(10):1995-2001. doi: 10.1016/0006-2952(93)90009-l.
Studies were carried out using a tetraphenylphosphonium (TPP+)-selective electrode to monitor the effect of selected calcium (Ca2+) antagonists and the dihydropyridine Ca2+ agonist Bay K8644 on membrane potential (psi) associated with isolated rat heart mitochondria. Verapamil and diltiazem (10-500 microM), standard Ca2+ antagonists, produced a depolarization of both liver and heart mitochondria at concentrations > 150 microM. In contrast, nitrendipine (10-200 microM), a dihydropyridine compound, produced a concentration-related inhibition of psi in mitochondria from both sources, effects which were statistically significant at concentrations > 50 microM. Cinnarizine (10-100 microM) and bepridil (10-100 microM) also produced inhibition of heart psi, these effects being particularly noted in the presence of bepridil, where depolarization of the membrane was statistically significant with only 10 microM drug. The results indicate the complexity of action of these drugs at the mitochondrial level. In general, drug actions on psi appear to be correlated with previously reported effects on Ca2+ transportation rather than oxidative phosphorylation associated with rat heart mitochondria. The findings also illustrate that the mitochondrial actions of cardiovascular compounds may be of relevance in situ, particularly during ischaemia/reperfusion when mitochondria become loaded with Ca2+.
采用四苯基鏻（TPP⁺）选择性电极进行研究，以监测所选钙（Ca²⁺）拮抗剂和二氢吡啶类Ca²⁺激动剂Bay K8644对与离体大鼠心脏线粒体相关的膜电位（ψ）的影响。维拉帕米和地尔硫䓬（10 - 500微摩尔）作为标准Ca²⁺拮抗剂，在浓度>150微摩尔时会使肝脏和心脏线粒体均发生去极化。相比之下，二氢吡啶类化合物尼群地平（10 - 200微摩尔）会对来自这两种来源的线粒体中的ψ产生浓度依赖性抑制，在浓度>50微摩尔时，这些影响具有统计学意义。桂利嗪（10 - 100微摩尔）和苄普地尔（10 - 100微摩尔）也会抑制心脏的ψ，在苄普地尔存在的情况下尤其明显，仅10微摩尔药物就能使膜去极化具有统计学意义。结果表明这些药物在线粒体水平的作用具有复杂性。一般来说，药物对ψ的作用似乎与先前报道的对Ca²⁺转运的影响相关，而非与大鼠心脏线粒体相关的氧化磷酸化。这些发现还表明心血管化合物的线粒体作用可能在原位具有相关性，特别是在缺血/再灌注期间，此时线粒体中会积累Ca²⁺。
