Altschuld R A, Hohl C M, Castillo L C, Garleb A A, Starling R C, Brierley G P
Department of Medical Biochemistry, Ohio State University College of Medicine, Columbus 43210-1218.
Am J Physiol. 1992 Jun;262(6 Pt 2):H1699-704. doi: 10.1152/ajpheart.1992.262.6.H1699.
Exchangeable intracellular Ca2+ as measured by 45Ca2+ uptake more than doubled when isolated adult rat ventricular cardiomyocytes were incubated 30 min with 8 microM cyclosporin; nevertheless the cells retained a normal rod-shaped morphology. High concentrations of ouabain caused a similar increase in 45Ca2+ uptake, but in this case the Ca2+ overload caused nearly all cells to hypercontract into a round disorganized form. The response to cyclosporin was concentration dependent with an apparent half-maximal effective concentration of 0.5 microM for enhancement of net 45Ca2+ accumulation. Verapamil (1 microM) could not inhibit this cyclosporin effect, but it was abolished by a 5-min preincubation with 12 microM crude ruthenium red. Cyclosporin also decreased the rate of 45Ca2+ efflux from prelabeled myocytes into Ca(2+)-containing and Ca(2+)-free media. These data are consistent with inhibition of mitochondrial 45Ca2+ efflux through the cyclosporin-sensitive mitochondrial inner membrane pore. It would appear that periodic transient increases in mitochondrial inner membrane permeability provide a pathway for mitochondrial Ca2+ extrusion under relatively normal conditions in isolated adult rat heart cells.
当分离的成年大鼠心室心肌细胞与8微摩尔环孢菌素一起孵育30分钟时，通过45Ca2+摄取测量的可交换细胞内Ca2+增加了一倍多；然而，细胞仍保持正常的杆状形态。高浓度的哇巴因导致45Ca2+摄取有类似增加，但在这种情况下，Ca2+超载导致几乎所有细胞过度收缩成圆形的无序形态。对环孢菌素的反应呈浓度依赖性，增强净45Ca2+积累的表观半数有效浓度为0.5微摩尔。维拉帕米（1微摩尔）不能抑制这种环孢菌素效应，但在与12微摩尔粗制钌红预孵育5分钟后，该效应被消除。环孢菌素还降低了预先标记的心肌细胞中45Ca2+向含Ca2+和不含Ca2+培养基中的流出速率。这些数据与通过环孢菌素敏感的线粒体内膜孔抑制线粒体45Ca2+流出一致。看来，线粒体内膜通透性的周期性短暂增加为分离的成年大鼠心脏细胞在相对正常条件下的线粒体Ca2+挤出提供了一条途径。
