Lancaster M K, Harrison S M
Department of Physiology, University of Leeds, UK.
Exp Physiol. 1998 May;83(3):349-60. doi: 10.1113/expphysiol.1998.sp004118.
Exposure of cardiac muscle to metabolic poisons reduces the availability of cellular ATP and cardiac dysfunction ensues. In this study rat ventricular myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were determined during metabolic blockade and following restoration of mitochondrial ATP production. Metabolic blockade resulted in a rapid failure of contractions and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and ultimately a rigor contracture. Washing out cyanide during the development of the rigor contracture led to a rapid relaxation of the contracture, a fall in cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were abolished in the presence of oligomycin. This suggests that the rapid partial recovery of cytosolic acidosis could result from the rephosphorylation of ADP to ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).
将心肌暴露于代谢毒物会降低细胞ATP的可用性，继而引发心脏功能障碍。在本研究中，将大鼠心室肌细胞暴露于2-脱氧葡萄糖、碘乙酸盐和氰化物中，以诱导完全代谢阻滞。在代谢阻滞期间以及线粒体ATP产生恢复后，测定收缩、胞质Ca2+和pH的变化。代谢阻滞导致收缩和Ca2+瞬变迅速衰竭、舒张期Ca2+升高、胞质酸中毒，最终导致强直收缩。在强直收缩发展过程中冲洗掉氰化物会导致挛缩迅速松弛、胞质Ca2+下降以及胞质酸中毒迅速部分逆转。在存在寡霉素的情况下，胞质酸中毒的部分逆转和胞质Ca2+的下降被消除。这表明胞质酸中毒的快速部分恢复可能是由于线粒体F1,F0-ATP酶将ADP重新磷酸化为ATP（该反应消耗质子）所致。
