Young W, Chen J, Jung F, Gardner P
Department of Medicine, Stanford University, California.
Mol Pharmacol. 1988 Sep;34(3):239-44.
The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine Ca antagonist nifedipine. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs.
通过流式细胞术评估二氢吡啶钙通道激动剂Bay K 8644对负载indo-1的Jurkat人白血病T淋巴细胞的作用。浓度为10(-9)至10(-4)M的Bay K 8644引起细胞内游离钙浓度呈剂量依赖性升高，二氢吡啶类钙拮抗剂硝苯地平未模拟出该效应。细胞外膜片钳技术的单通道记录表明，Bay K 8644激活了一个8-pS的钡通透通道，该通道以短暂事件爆发的形式开放。该通道似乎与先前描述的参与T细胞活化的电压不敏感、信使介导的钙通透通道相同。Bay K 8644对这些通道的主要作用是增加通道重新开放的概率，显然对平均通道开放时间没有重大影响。结果表明，二氢吡啶类钙激动剂Bay K 8644与电压门控和受体操纵的钙通道均相互作用，也为开发新型免疫调节药物提供了潜在策略。
