心力衰竭患者M_2乙酰胆碱受体的自身抗体对豚鼠心肌细胞L型钙通道的影响  

Effect of serum autoantibodies against the M_2 muscarinic acetylcholine receptors from patients with heart failure on L-Type Ca^(2+) channel activity in guinea pig cardiac myocytes

作　　者：缪国斌[1] 刘瑾春[1] 王树岩[1] 刘秀兰[1] 张健[1] 张麟[1] 

机构地区：[1]首都医科大学附属北京朝阳医院综合科,100020

出　　处：《中华心血管病杂志》2006年第6期537-540,共4页Chinese Journal of Cardiology

基　　金：国家863课题子课题"扩张型心肌病致病基因与相关基因的研究"(2002BA711A07)

摘　　要：目的观察心力衰竭患者M2乙酰胆碱能受体的自身抗体(Abs)阳性血清以及M2乙酰胆碱能受体激动剂碳酰胆碱对心肌细胞的影响。方法应用全细胞钳制技术,定量观察并比较碳酰胆碱和心力衰竭患者Abs阳性血清对豚鼠单个心室肌细胞的L型钙电流强度的影响。结果M2受体激动剂碳酰胆碱使预先由异丙肾上腺素增大的L型钙电流峰值电流强度和标准电流密度从(2111.65±203.13)pA和(18.83±1.14)pA/pF下降为(1230.87±208.14)pA(P<0.01)和(10.72±1.06)pA/pF(P<0.01),M2受体阻滞剂阿托品可以阻断碳酰胆碱的这一作用。同样,心力衰竭患者的Abs阳性血清能使L型钙电流的峰值电流强度由(1995.21±195.13)pA下降至(636.42±110.07)pA,P<0.01,标准电流密度由(18.13±1.03)pA/pF下降至(5.54±0.81)pA/pF,P<0.01;阿托品也可阻断此作用。结论心力衰竭患者Abs阳性血清对豚鼠心室肌细胞的作用与碳酰胆碱相似,对心肌细胞M2受体有“激动剂样”效应,能使心肌细胞的L型钙电流减小,产生负性肌力作用;阿托品可以阻断它们对豚鼠心室肌细胞的作用。Objective To investigate the effect of serum autoantibodies against the human M2 muscarinic acetylcholine receptors （M2-receptors, Abs） from patients with congestive heart failure on L- Type Ca^2＋channel activity in guinea pig cardiac myocytes. Method Using whole cell patch-clamp technique, we quantitatively measured the ionic intensity and density of L-Type Ca^2＋channel （ICa-L ）. Results The M2-receptors agonist （carbachol） could decrease the ICa-L peak intensity and density stimulated by isoprenaline from （2111.65 ± 203.13 ） pA and （ 18.83 ± 1.14 ） pA/pF to （ 1230. 87 ± 208. 14）pA（P〈0.01） and （10.72 ±1.06） pA/pF （P〈0.01）. The serum Abs could also decrease ICa-L peak intensity and density [from （1995.21 ± 195. 13） pA and （18. 13 ± 1.03） pA/pF to （636.42 ± 110. 07） pA（P 〈0.01 ） and （5.54 ±0. 81 ）pA/pF, P 〈0.01 ]. The M2-receptors antagonist, atropine was able to block these effects of carbachol and Abs. Conclusions The circulating serum autoantibodies against the M2-receptors has similar effect as M2-receptors agonist on decreasing the isoprenaline stimulated ICa-L in guinea pig cardiac myocytes and posses negative inotropic effect. These results further suggest that serum autoantibodies against the human M2 muscarinic acetylcholine receptors may participate in the pathophysiological processes in patients with heart failure.

关 键 词：心力衰竭 充血性 自身抗体 受体 胆碱能 钙通道 

分 类 号：R541.6[医药卫生—心血管疾病]