Tang T, Duffield R, Ho A K
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, 61605, USA.
Eur J Pharmacol. 1998 Nov 6;360(2-3):205-11. doi: 10.1016/s0014-2999(98)00657-8.
The effects of the L-type (nifedipine and verapamil) and the T-type (mibefradil) Ca2+ channel blockers on the increase in intracellular Ca2+ concentration ([Ca2+]i) induced by NaCN metabolic inhibition and hyperkalemia were examined in chicken cardiomyocytes using fluorescence imaging with Fura-2. NaCN induced a slow and sustained rise in [Ca2+]i, which was not affected by pretreating the cells for 5 min with nifedipine, verapamil, or mibefradil at 100 nM or 10 microM. Pretreatment of the cells with 10 microM nifedipine, verapamil, or mibefradil for 5 min remarkably inhibited the K+-induced increase in [Ca2+]i. These inhibitory effects diminished after 48-h pretreatment with nifedipine or verapamil but not with mibefradil. Ryanodine also induces an increase in [Ca2+]i, and this effect was enhanced by 48-h pretreatment of the cells with 10 microM verapamil but not with 10 microM mibefradil. We conclude that the NaCN-induced increase in [Ca2+]i is independent of the Ca2+ influx though the L-type or T-type Ca2+ channels. Chronic inhibition of the L-type Ca2+ channels but not T-type channels may enhance the ryanodine receptor-mediated Ca2+ release, which may be responsible for the development of tolerance to their inhibitory effects on K+-induced increase in [Ca2+]i.
利用Fura-2荧光成像技术，在鸡心肌细胞中研究了L型（硝苯地平和维拉帕米）和T型（米贝拉地尔）钙通道阻滞剂对由氰化钠代谢抑制和高钾血症诱导的细胞内钙离子浓度（[Ca2+]i）升高的影响。氰化钠诱导[Ca2+]i缓慢且持续升高，在100 nM或10 μM的硝苯地平、维拉帕米或米贝拉地尔预处理细胞5分钟后，此升高不受影响。用10 μM硝苯地平、维拉帕米或米贝拉地尔预处理细胞5分钟可显著抑制钾离子诱导的[Ca2+]i升高。在用硝苯地平或维拉帕米预处理48小时后，这些抑制作用减弱，但用米贝拉地尔预处理则不然。Ryanodine也可诱导[Ca2+]i升高，用10 μM维拉帕米预处理细胞48小时可增强此效应，但用10 μM米贝拉地尔预处理则不然。我们得出结论，氰化钠诱导的[Ca2+]i升高与通过L型或T型钙通道的钙离子内流无关。长期抑制L型钙通道而非T型钙通道可能会增强ryanodine受体介导的钙离子释放，这可能是对它们抑制钾离子诱导的[Ca2+]i升高产生耐受性的原因。
