T型钙通道在心肌肥厚大鼠心肌细胞钙内流中的作用

T-type calcium channels contribute to calcium influx in myocytes of rats with hypertrophic heart

目的研究T型钙通道在心肌细胞钙离子内流中的作用及其对心脏兴奋收缩耦联的可能影响。方法测定选择性T型钙通道阻滞剂米贝拉地尔对培养的SD乳大鼠心室肌细胞和二肾一夹心肌肥厚大鼠心室肌细胞[Ca2+]i的影响。结果血管紧张素Ⅱ(AngⅡ)刺激使乳大鼠心室肌舒张期细胞[Ca2+]i增高,收缩期细胞[Ca2+]i降低,[Ca2+]i上升和下降的时间延长。米贝拉地尔1.25～5μmol·L-1浓度依赖性降低AngⅡ引起的细胞[Ca2+]i变化。在心肌肥厚模型大鼠,咖啡因刺激后,[Ca2+]i增幅和最高[Ca2+]i明显降低。而米贝拉地尔25mg·kg-1·d-1(灌胃给药7～9周)组加入咖啡因刺激后细胞内[Ca2+]i增幅和最高[Ca2+]i明显增高。结论T型钙通道异常开放可以引起心肌细胞内钙超载。阻断T型钙通道,可能通过改善肌浆网摄取及释放钙的功能而抑制心肌细胞钙超载。

AIM To study the effect of T-type calcium channels in calcium influx of cardiomyocyte and the possible influence to excitation-contraction coupling. METHODS Effects of mibefradil, a selective T-type channel blocker, on intracellular concentration of calcium （[Ca^2＋]i） in cultured newborn rat ventricular cells treated by angiotensin Ⅱ （Ang Ⅱ） and ventricular myocytes of rat with hypertrophic heart induced by two-kidney one clip were recorded. RESULTS The diastolic [Ca^2＋]i raised and systolic [Ca^2＋]i dropped in cultured neonatal rat ventricular cells when stimulated with Ang Ⅱ. At the same time, the ascending and descending time of [Ca^2＋]i was also delayed. Mibefradil 1.25 - 5 μmol·L^-1 reduced the change in [Ca^2＋]i induced by Ang Ⅱ in a concentration-dependent mariner. In ventricular myocytes of rat with hypertrophic heart, the maximum [Ca^2＋]i and increment of [Ca^2＋]i decreased significantly after stimulated with caffeine, while mibefradil （25 mg·kg^-1·d^-1, ig, for 7-9 weeks） treatment increased that significantly after stimulated with caffeine. CONCLUSION The abnormal open of T-type calcium channel can induce calcium over-load in cardiomyocytes. Block of T-type calcium channel may inhibit the calcium over-load by improving the function of releasing and absorbing calcium of sarcoplasmic reticulum.