Angiotensin II decreases neuronal delayed rectifier potassium current: Role of calcium/calmodulin-dependent protein kinase II

作     者：Zhu, MY Gelband, CH Posner, P Sumners, C 

作者机构：Univ Florida Coll Med Dept Physiol Gainesville FL 32610 USA Univ Florida Inst Brain Gainesville FL 32610 USA 

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

年 卷 期：1999年第82卷第3期

页      面：1560-1568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] 

基　　金：NHLBI NIH HHS [HL-49130] Funding Source: Medline NINDS NIH HHS [NS-19441] Funding Source: Medline 

主　　题：血管紧张素Ⅱ/药理学 血管紧张素Ⅱ/生理学 钙-钙调素依赖性蛋白激酶2型 钙-钙调素依赖性蛋白激酶类/拮抗剂和抑制剂 钙-钙调素依赖性蛋白激酶类/生理学 钙调蛋白/拮抗剂和抑制剂 延迟整流钾通道 导电性 酶激活/生理学 神经元/代谢 钾通道阻滞剂 钾通道/药物作用 钾通道/生理学 钾通道 电压门控 蛋白激酶C/拮抗剂和抑制剂 蛋白激酶C/代谢 大鼠 Sprague-Dawley 受体 血管紧张素 1型 受体 血管紧张素 2型 受体 血管紧张素/生理学 动物 大鼠 

摘      要：Angiotensin II(Ang II) acts at specific receptors located on neurons in the hypothalamus and brain stem to elicit alterations in blood pressure, fluid intake, and hormone secretion. These actions of Ang II. are mediated via Ang II type 1 (AT(1)) receptors and involve modulation of membrane ionic currents and neuronal activity. In previous studies we utilized neurons cultured from the hypothalamus and brain stem of newborn rats to investigate the AT(1) receptor-mediated effects of Ang II on neuronal K+ currents. Our data indicate that Ang II decreases neuronal delayed rectifier (Kv) current, and that this effect is partially due to activation of protein kinase C (PKC),specifically PKC alpha. However, the data also indicated that another Ca2+-dependent mechanism was also involved in addition to PKC. Because Ca2+/calmodulin-dependent protein kinase II (CaM KII) is a known modulator of K+ currents in neurons, we investigated the role of this enzyme in the AT(1) receptor-mediated reduction of neuronal Ky current by Ang II. The reduction of neuronal Ky current by Ang II was attenuated by selective inhibition of either calmodulin or CaM KII and was mimicked by intracellular application of activated (autothiophosphorylated) CaM KII alpha. Concurrent inhibition of CaM KII and PKC completely abolished the reduction of neuronal Ky by Ang II. Consistent with these findings is the demonstration that Ang II increases CaM KII activity in neuronal cultures, as evidenced by increased levels of autophosphorylated CaM KII alpha subunit. Last, single-cell reverse transcriptase (RT)-PCR analysis revealed the presence of AT(1) receptor-, CaM KII alpha-, and PKC alpha subunit mRNAs in neurons that responded to Ang II with a decrease in Ky current. The present data indicate that the AT(1) receptor-mediated reduction of neuronal Ky current by Ang II involves a Ca2+/calmodulin/CaM KII pathway, in addition to the previously documented involvement of PKC.