Schneider A S, Cline H T, Rosenheck K, Sonenberg M
J Neurochem. 1981 Sep;37(3):567-75. doi: 10.1111/j.1471-4159.1982.tb12524.x.
The catecholamine secretory function of a preparation of isolated bovine adrenal chromaffin cells has been further characterized under conditions designed to elucidate the mechanism of calcium channel activation and the possible role of cytoskeletal elements in stimulus-secretion coupling. Three related sets of data were obtained: (1) Differences in kinetics, Ca dependence, strength, and additivity of the secretory response to acetylcholine (ACh) versus excess K; (2) the effects on secretion of the Ca channel-blocking agents, Ni, Mg, and verapamil; and (3) the Ca dependence of vinblastine action on ACh- and K-evoked secretion. The results suggest that a major portion of the Ca influx required for catecholamine release enters the cell via voltage-dependent Ca channels with some additional Ca influx via the ACh receptor channel. Comparison of the present secretion data with corresponding known electrophysiological properties of isolated chromaffin cells provides added evidence for a role of chromaffin cell action potentials in regulation of Ca influx and the secretory response. Elevated Ca concentrations enhanced K-evoked secretion to levels comparable to that of Ach but did not induce a vinblastine block of K-evoked release. This provides further evidence against a role of microtubules in the common exocytosis event per se. However, a role of cytoskeletal elements in directing the movement of secretory granules, or an action of vinblastine at cholinergic receptors, remain distinct possibilities.
在旨在阐明钙通道激活机制以及细胞骨架成分在刺激-分泌偶联中可能作用的条件下,对分离的牛肾上腺嗜铬细胞制剂的儿茶酚胺分泌功能进行了进一步表征。获得了三组相关数据:(1)对乙酰胆碱(ACh)与过量钾的分泌反应在动力学、钙依赖性、强度和加和性方面的差异;(2)钙通道阻滞剂镍、镁和维拉帕米对分泌的影响;(3)长春碱对ACh和钾诱发分泌作用的钙依赖性。结果表明,儿茶酚胺释放所需的大部分钙内流通过电压依赖性钙通道进入细胞,还有一些额外的钙通过ACh受体通道内流。将目前的分泌数据与分离的嗜铬细胞相应已知的电生理特性进行比较,为嗜铬细胞动作电位在调节钙内流和分泌反应中的作用提供了更多证据。升高的钙浓度将钾诱发的分泌增强到与ACh相当的水平,但并未诱导长春碱对钾诱发释放的阻断。这进一步证明微管本身在常见的胞吐事件中不起作用。然而,细胞骨架成分在引导分泌颗粒运动中的作用,或长春碱在胆碱能受体处的作用,仍然是明显的可能性。