Differential effects of calcium antagonists on viability of adult rat ventricular myocytes.
Differential effects of calcium antagonists on viability of adult rat ventricular myocytes.
复制标题
钙拮抗剂对成年大鼠心室肌细胞活力的不同影响。
DOI：
10.1016/s0022-2828(85)80109-7
复制
发表时间：
1985
影响因子：
5
通讯作者：
Bassett,AL
中科院分区：
文献类型：
--
作者：
Miller,LS;Barrett,JN;Cameron,JS;Bassett,AL
本研究旨在确定不同类别的 Ca2+ 通道阻滞剂对缺氧（100% N2）条件下暴露于高 K+ 的离体成年大鼠心室肌细胞是否具有不同的保护作用。耐钙肌细胞在对照 (4 mmK+) 有氧条件下孵育，然后接受高 K+ (75 mm) 和 N2。通过形态学标准（即不存在起泡、颗粒化等）、ATP水平的维持、台盼蓝的排除以及自发收缩活性的存在或不存在来评估细胞。在对照条件下，细胞处于静止状态，并以约 10%/h 的速度下降。在没有氧气的情况下，细胞衰退的速度明显加快。在这些条件下，维拉帕米、地尔硫卓和二氢吡啶对细胞衰退没有显着影响。暴露于75 mmK0+的细胞在缺氧条件下表现出收缩活性并加快衰退速度；这些影响与将 Na0+ 降低至 75 mm 无关。高 K0+ 和 N2 中的细胞受到维拉帕米的显着保护（即收缩活性和下降率降低），地尔硫卓的保护效果较差，二氢吡啶则完全没有保护。维拉帕米或地尔硫卓对高 K0+ 细胞的 45 Ca2+ 摄取没有显着改变。咖啡因诱导高K0+培养细胞的收缩活性立即停止，但不影响缺氧条件下细胞衰退的加速速度。维拉帕米和地尔硫卓在这种非跳动细胞制剂中仍然具有显着的保护作用。维拉帕米和地尔硫卓对带皮心脏细胞的振荡频率均没有任何影响。数据表明，根据其作用位点和机制，不同类别的 Ca2+ 拮抗剂可以在病理生理条件下对细胞产生不同的影响。维拉帕米和地尔硫卓可能作用于去极化细胞的肌膜膜，其位点与 Na+/Ca2+ 交换载体和快速失活的 Ca2+ 通道无关。
This study was designed to determine whether the various classes of Ca2+channel blockers have differential protective effects on isolated adult rat ventricular myocytes exposed to high K+under anoxic (100% N2) conditions. Calcium-tolerant myocytes were incubated under control (4 mmK+) aerobic conditions and then subjected to high K+(75 mm) and N2. The cells were assessed by morphological criteria (i.e. absence of blebbing, granulation etc.), maintenance of ATP levels, exclusion of trypan blue, and the presence or absence of spontaneous contractile activity. Under control conditions, the cells were quiescent and declined at a rate of ≈10%/h. In the absence of O2, the rate of cell decline was significantly faster. Verapamil, diltiazem and the dihydropyridines had no significant effects on cell decline under these conditions. Cells exposed to 75 mmK0+exhibited contractile activity and accelerated rate of decline under anoxic conditions; these effects were independent of lowering Na0+to 75 mm. Cells in high K0+and N2were significantly protected (i.e. contractile activity and rate of decline were decreased) by verapamil, less so by diltiazem, and not at all by the dihydropyridines.The uptake of45Ca2+into cells in high K0+was not significantly altered by verapamil or diltiazem. Caffeine induced the immediate cessation of contractile activity of cells incubated in high K0+, but did not affect the accelerated rate of cell decline under anoxic conditions. Verapamil and diltiazem still conferred significant protection in this non-beating cell preparation. Neither verapamil nor diltiazem had any effect on the oscillation frequency of skinned heart cells. The data indicate that, based on their sites and mechanisms of action, the various classes of Ca2+antagonists can differentially affect cells under pathophysiological conditions. Verapamil and diltiazem may act at the sarcolemmal membrane of depolarized cells at sites independent of the Na+/Ca2+exchange carrier and the fast inactivating Ca2+channel.