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氧化苯胂对大鼠心室肌细胞L 型Ca2+ 电流的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2002年第2期
页码:
89-91，94
栏目:
实验研究
出版日期:
2002-03-01

文章信息/Info

Title:
Effect of phenylarsine oxide on L- type calcium channel currents inisolated ventricular myocytes
作者:
董　玲1;  周士胜1;  高　瞻1;  臧益民1;  杨安钢2;  王跃民1;  马　恒1
第四军医大学: 1. 生理学教研室; 2. 生物化学教研室, 陕西 西安 710032
Author(s):
DONG Ling 1;  ZHOU Shi-sheng 1;  GAO Zhan1;  ZANG Yi-min1;  YANG An-gang2;  WANG Yao2
1.Department of Physiology, 2. Department of Biochemistry, Fourth Military Medical University, Xi’an Shaanxi 710032, China
关键词:
氧化苯胂;  钙电流;  心室肌细胞
Keywords:
phenylarsine oxide;  L-type Ca2+ current;  ventricular myocyte
分类号:
Q463
DOI:
-
文献标识码:
A
摘要:
目的 探讨氧化苯胂(PAO ) , 一种膜可通透的酪氨酸磷酸酶抑制剂, 对大鼠心室肌细胞L 型Ca2+ 电流( ICa,L )的影响。方法 采用全细胞膜片钳技术记录大鼠心室肌细胞ICa,L。结果 ①PAO 对基础ICa,L 及β-肾上腺素受体激动剂异丙肾上腺素( Iso) 激发的ICa,L 有抑制作用; ②PAO 对腺苷酸环化酶激动剂forskolin 激发的ICa,L 亦有抑制作用;③电极内液加入1. 5mmol/L 矾酸钠不能消除PAO 的作用; ④PAO 对ICa,L 的抑制作用可被二硫代苏糖醇反转。结论 PAO 抑制ICa,L 的作用与cAMP-PKA-磷酸化途径和酪氨酸磷酸酶无关, 可能与其使L 型Ca2+ 通道蛋白上巯基氧化有关。
Abstract:
AIM To investigate the effect of phenylarsine oxide (PAO ) , one of membrane permeatable tyrosine phosphatase inhibitors, on the L-type calcium channel currents ( ICa,L ) in isolated ventricular myocytes. METHODS ICa,L was recorded by using the whole cell voltage clamp technique. RESULTS PAO suppressed basal or isoproterenol ( Iso ) -activated ICa,L. Inhibition of forskolin-activated ICa,L by PAO was also observed. PAO was effective even in the presence of intrapipette sodium orthovanadate, a tyrosine phosphatase inhibitor. Dithiothreitol, a reducing agent, reversed the effect of the inhibition of PAO on the currents. CONCLUSION PAO inhibits ICa,L is probably an oxidative effect directly on the-SH of the Ca2+ channels.

参考文献/References

[1] Bers DM , Perez-Reyes E. Ca channels in cardiac myocytes:structure and function in Ca influx and intracellular Ca release[J]. Cardiovasc Res, 1999, 42 (2) : 339- 360.

[2] Herzig S, Neumann J. Effects of serine/threonine protein phosphatases on ion channels in excitable membranes [J]. Physiol Rev, 2000, 80 (1) : 173- 210.

[3] Sims C, Chiu J , Harvey RD. Tyrosine phosphatase inhibitors selectively antagonize beta-adrenergic receptor-dependent regulation of cardiac ion channels [J]. Mol Pharmacol, 2000, 58(6) : 1213- 1221.

[4]Wijetunge S, Lymn JS, Hughes AD. Effect of inhibition of tyrosine phosphatases on voltage-operated calcium channel currents in rabbit isolated ear artery cells [J]. Br J Pharmacol,1998, 124 (2) : 307- 316.

[5] Zhou SS, TakaiA , Tominaga M , et al. Phosphatase-mediated enhancement of cardiac cAMP-activated Cl- channel blocker,anth racene-9-carboxylate [J]. Circ Res, 1997, 81 (2) : 219-228.

[6] Hescheler J , Kameyama M , Trautwein W , et al. Regulation of the cardiac calcium channel by protein phosphatases [J]. Eur J Biochem , 1987, 165 (2) : 261- 266.

[7] Yamaoka K, Yakehiro M , Yuki T, et al. Effect of sulfhydryl reagents on the regulatory system of the L-type calcium channel in frog ventricular myocytes [J]. Pfluegers Arch, 2000,440 (2) : 207- 215.

备注/Memo

备注/Memo:
收稿日期：2001-09-04.基金项目: 本课题由国家自然科学基金(No. 39870381)、国家教委留学回国人员启动基金, 长江学者匹配骨干教师基金和军队杰出中轻年人才基金资助
更新日期/Last Update: 2002-03-01