Calcium release from internal stores is required for the generation of spontaneous hyperpolarizations in dopaminergic neurons of neonatal rats

作     者：Seutin, V Mkahli, F Massotte, L Dresse, P 

作者机构：Univ Liege Pharmacol Lab Tour Pathol B23 B-4000 Sart I Belgium 

出 版 物：《JOURNAL OF NEUROPHYSIOLOGY》 (神经生理学杂志)

年 卷 期：2000年第83卷第1期

页      面：192-197页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

主　　题：动物 新生 蜂毒明肽/药理学 脑/生理学 咖啡因/药理学 钙/代谢 钙转运ATP酶类/拮抗剂和抑制剂 丹曲林/药理学 多巴胺/生理学 酶抑制剂/药理学 诱发电位/药物作用 吲哚类/药理学 神经元/药物作用 神经元/生理学 大鼠 Sprague-Dawley 大鼠 Wistar 兰尼碱/药理学 动物 大鼠 

摘      要：We recently have demonstrated the existence of spontaneous hyperpolarizations in midbrain dopaminergic neurons of neonatal but not adult rats. These events are mediated by the opening of apamin-sensitive K+ channels after a rise in the intracellular concentration of Ca2+ They are resistant to tetrodotoxin in most cases and are probably endogenous (i.e., not synaptically activated). Here their mechanism was investigated. Cyclopiazonic acid (10 mu M), a specific inhibitor of endoplasmic reticulum Ca2+ ATPases, reversibly abolished the events. Caffeine, which promotes Ca2+ release from intracellular stores, had concentration-dependent effects. At 1 mM, it markedly and steadily increased the frequency and the amplitude of the hyperpolarizations. At 10 mM, it induced a transient increase in their frequency followed by their cessation. All these effects were quickly reversible. Ryanodine (10 mu M), which decreases the conductance of Ca2+ release channels, irreversibly blocked the spontaneous hyperpolarizations. Dantrolene (100 mu M), a blocker of Ca2+ release from sarcoplasmic reticulum of striated muscle, did not affect the events. On the other hand, Cd2+ (100-300 mu M), a broad antagonist of membrane voltage-gated Ca2+ channels, significantly reduced the amplitude and the frequency of the hyperpolarizations. However, when the frequency of the events was increased by 1 mM, caffeine, Cd2+ affected them to a smaller extent, whereas cyclopiazonic acid still abolished them. We conclude that internal stores are the major source of Ca2+ ions that induce the K+ channel openings underlying the spontaneous hyperpolarizations of these neurons.