Artalejo C R, Adams M E, Fox A P
Northwestern University, Department of Neurobiology and Physiology, Evanston, Illinois 60208.
Nature. 1994 Jan 6;367(6458):72-6. doi: 10.1038/367072a0.
To determine whether the different types of Ca2+ channels present in the same secretory cell contribute equally to secretion, we used chromaffin cells to analyse the coupling between three distinct types of Ca2+ channel and exocytosis. These are omega-conotoxin-GVIA-sensitive N-type channels, omega-agatoxin-IVA-sensitive P-type Ca2+ channels and dihydropyridine-sensitive facilitation Ca2+ channels, which are normally quiescent but are activated by depolarizing pre-pulses, repetitive depolarizations to physiological potentials, or agents that raise cyclic AMP. We have simultaneously monitored changes in capacitance as an assay of catecholamine secretion, and Ca2+ currents. Although all three types of Ca2+ channel trigger secretion individually, facilitation channels produce much greater secretion for a given size of Ca2+ current, indicating that they are coupled more efficiently to exocytosis. These results indicate that facilitation Ca2+ channels may be physically nearer vesicle release sites. They also show that low efficiency P- and N-type channels could trigger mild release and that high-efficiency facilitation channels may underlie the massive catecholamine release that occurs during the 'fight or flight' response.
为了确定同一分泌细胞中存在的不同类型Ca2+通道对分泌的贡献是否相同,我们利用嗜铬细胞分析了三种不同类型Ca2+通道与胞吐作用之间的偶联。它们分别是对ω-芋螺毒素-GVIA敏感的N型通道、对ω-阿加毒素-IVA敏感的P型Ca2+通道以及对二氢吡啶敏感的易化性Ca2+通道,后者通常处于静息状态,但可被去极化预脉冲、向生理电位的重复去极化或升高环磷酸腺苷的试剂激活。我们同时监测了作为儿茶酚胺分泌检测指标的电容变化以及Ca2+电流。虽然所有三种类型的Ca2+通道均可单独触发分泌,但对于给定大小的Ca2+电流,易化性通道产生的分泌要多得多,这表明它们与胞吐作用的偶联效率更高。这些结果表明,易化性Ca2+通道可能在物理位置上更靠近囊泡释放位点。它们还表明,低效率的P型和N型通道可能触发轻度释放,而高效率的易化性通道可能是“战斗或逃跑”反应期间大量儿茶酚胺释放的基础。