SODIUM-DEPENDENT SECRETION AND RETENTION OF NE IN ADRENERGIC TERMINALS

肾上腺素能末梢中钠依赖的 NE 分泌和保留

• 批准号: 3858083
• 负责人: D F BOGDANSKI
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858083
• 关键词: adrenergic receptor; axon; calcium; calcium channel; heart; laboratory rat; norepinephrine; secretion; sodium; voltage gated channel

The following report represents continued research on a functional, physiologic neurosecretory system. Sodium can regulate a delayed, Ca-evoked, export-mediated secretion of [3H]norepinephrine ([3H]NE) in the adrenergic terminals in slices of rat heart. The secretion was interpreted to be an indication of Ca permeation through specific channels in the axolemma. Permeation through other channels did not necessarily evoke secretion. Secretion occurred in a medium (Ch-Ca) in which choline (not Li, K or sucrose) replaced the Na in a Krebs-bicarbonate medium. Choline in a limited way functioned a surrogate for Na as an extracellular requirement for retention. Like Na (Bogdanski and Brodie, 1969) choline (25 and 50 mM) in a sucrose medium inhibited the non-Ca dependent depletion of the [3H]NE. The choline (13OmM) in Ch-Ca, after a delay of 60 to 80 min, permitted Ca to evoke secretion. Its start was related to the length of the time period that the terminals had been exposed to choline, not Ca. Because secretion was prevented by Mn, lmM, it was concluded that a voltage regulated Ca channel might finally have opened. Secretion was stopped more rapidly after Na was added to the Ch-Ca than after the terminals were transferred to a Ca-deprived medium. Na thus appeared to act intracellularly. K (66mM) augmented maximal rates of secretion evoked by Ch-Ca with or without added Na. Apparently, the axolemma in Ch-Ca had been polarized and depolarization by K opened new Ca channels. Conclusions: Na at two or more sites in or proximate to the axolemma may partially regulate physiological secretion. First, choline representing physiological Na temporarily prevented spontaneous Ca entry through channels specific for secretion. This did not involve Na-Ca exchange. Second, Na in the axosol inhibited secretion. Malfunctions of either function could induce physiologically excessive, spontaneous release of transmitters.

以下报告代表了对一个功能， 生理性神经分泌系统 钠可以调节延迟的， 钙诱发的，输出介导的[3 H]去甲肾上腺素（[3 H]NE）分泌， 大鼠心脏切片中的肾上腺素能末梢。 分泌物是 解释为指示Ca通过特定的 轴膜中的通道。 通过其他渠道的渗透并没有 必然会引起分泌。 分泌发生在培养基（Ch-Ca）中， 其中胆碱（不是Li，K或蔗糖）取代了Na， Krebs-碳酸氢盐培养基。 胆碱以有限的方式发挥作用， Na的替代物作为细胞外滞留的需要。 如Na （Bogdanski和Brodie，1969）蔗糖培养基中的胆碱（25和50 mM） 抑制非Ca依赖性的[3 H]NE耗竭。 胆碱 （130 mM）在Ch-Ca中，延迟60至80分钟后， 分泌物 它的开始与时间的长短有关， 末梢接触的是胆碱而不是钙 因为分泌物是 阻止锰，1 mM，得出结论，电压调节钙 渠道终于可以打开了。 分泌停止得更快 在Ch-Ca中加入Na后， 去钙培养基中。 因此，Na似乎在细胞内起作用。 K （66 mM）增加Ch-Ca诱发的最大分泌速率， 不添加Na。 显然，Ch-Ca中的轴膜已经极化， 钾离子去极化开放了新的钙通道。 结论：Na在2 在轴膜中或接近轴膜的一个或多个位点可以部分调节 生理分泌 首先，胆碱代表生理钠 暂时阻止了自发性钙离子通过特异性通道进入， 分泌物 这不涉及钠钙交换。 第二，纳在 axosol抑制分泌。 任何一个功能的故障都可能导致 生理上过度的，自发释放的递质。