心房颤动时心房肌细胞L型Ca^(2+)通道与肌浆网间Ca^(2+)信号转导的探讨  

An approach to calcium signal transmission between L - type calcium channel and sarcoplasmic reticulum of atrial myocytes during atrial fibrillation

作　　者：刘元生[1] 郭继鸿[1] 许原[1] 张海澄[1] 李学斌[1] 张幼怡[2] 袁兰[3] 

机构地区：[1]北京大学人民医院心内科,北京100044 [2]北京大学第三医院血管研究所 [3]北京大学医学部激光共聚焦显微镜室,北京100083

出　　处：《中国病理生理杂志》2005年第10期1927-1929,共3页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30271431);北京大学985项目;北京市自然科学基金资助项目(No.7032030);首都医学发展科研基金资助项目(No.20023036)

摘　　要：目的:探讨房颤时心房肌细胞膜上L型Ca2+通道与肌浆网之间的Ca2+信号转导。方法:杂种犬10 条,随机分为正常对照组和单纯房颤组。房颤组用起搏器行右心房快速起搏(500±20)次／分,术后观测24周。正常 对照组不植入起搏器。胶原酶Ⅱ型分离心房肌细胞,用激光共聚焦显微镜检测L型Ca2+通道对细胞内Ca2+浓度变 化的影响;L型Ca2+通道与肌浆网三磷酸肌醇受体(IP3R)和兰尼碱受体(RyR)之间的Ca2+信号转导。结果:(1)L型 Ca2+通道与肌浆网IP3R之间的Ca2+信号转导:正常对照组、单纯房颤组的心房肌细胞在用mibefradil和丁卡因分别 阻滞T型Ca2+通道和RvR后给予细胞膜激动剂时,细胞内Ca2+浓度均升高(分别为1．4000±0．0776和1．5169± 0．4414),组间比较无显著差异(P>0．05);(2)L型Ca2+通道与肌浆网RyR之间的Ca2+信号转导:正常对照组的心房 肌细胞在用mibefradil和肝索分别阻滞T型Ca2+通道和IP3R后给予细胞膜激动剂时,细胞内Ca2+浓度升高(1．5576± 0．1989),单纯房颤组的细胞内Ca2+浓度也升高(1．5372±0．2952),两组间比较元显著差异(P>0．05)。结论:房颤时 L型Ca2+通道与RyR和IP3R之间可能存在信号转导,但其可能在房颤时的细胞内Ca2+超载及异常Ca2+信号转导方 面不起重要作用。AIM： To inquire into the Ca^2＋ signal transmission from L- type calcium channel to the sarcoplasma reticulum in atrial fibrillation. METHODS： Ten adult crossbred dogs were used in the experiment. Five dogs underwent continuous rapid atrial pacing （500±20 beats/min） for twenty - four weeks to create persistent atrial fibrillation. Another group of sizematched dogs （ n = 5） without pacemaker implantation was used as a control group. Canine atrial myocytes were isolated by enzymatic dissociation. The Ca^2＋ cytosolic transient in atrial myocytes was analyzed by confocal imaging after loading myocytes with the acetoxymethyl ester of fluo- 3 （Fluo-3/AM）. Ca^2＋ signal transmission from L- type Ca^2＋ channels in the plasma membrane to the sarcoplasma reticular IP3R and RyR in atrial myocytes during atria fibrillation were measured. RESULTS： （1） Ca^2＋ signal transmission from L- type calcium channel to IP3R in the sarcoplasma reticulum： intracellular Ca^2＋ concentration was slightly increased in two groups after blocking T - type calcium channel and RyR, but showed no statistic significance （ P 〉 0.05） between them. （2） Ca^2＋ signal transmission from L - type calcium channel to RyR in the sarcoplasma reticulum： intracellular Ca^2＋ concentration was risen （1.5576±0.1989） in control groups after blocking T- type calcium channel and IP3R, and no significance was observed （ P 〉 0.05） compared with that in atrial fibrillation group （ 1.5372 ± 0.2952）. CONCLUSIONS： Ca^2＋ signal transmission possibly exists from L- type calcium channel to RyR and IP3R in the sarcoplasma reticulum, but it does not play an important role in intracellular Ca^2＋ - overload and abnormal Ca^2＋ signal transmission during atrial fibrillation.

关 键 词：心房颤动 钙通道 信号转导 受体 兰尼碱 受体 肌醇1 4 5-三磷酸 

分 类 号：R363[医药卫生—病理学]