PTC124不影响豚鼠心室肌细胞的电生理特性  

The Chemical Compound PTC124 Does Not Affect Cellular Electrophysiology of guinea pig Ventricular Myocytes

作　　者：滕思勇[1] 黄健[1] 郝杰[1] 杜忠鹏[1] 浦介麟[1] 惠汝太 

机构地区：[1]中国医学科学院阜外心血管病医院,心血管疾病国家重点实验室,北京100037

出　　处：《中国分子心脏病学杂志》2012年第6期360-362,共3页Molecular Cardiology of China

基　　金：国家自然科学基金资助(30971176)

摘　　要：目的无义突变产生提早出现的终止密码子(Premature termination codon,PTC),其主要致病机制是突变基因单倍体表达不足,见于心脏钠通道SCN5A基因。SCN5A无义突变导致心脏传导功能障碍、扩张性心肌病和Brugada综合征(BrS)等疾病,目前尚无有效方法根治这类疾病,但药物将是治疗这类突变相关性疾病的最佳选择。近年来开发的口服药物PTC124,能够选择地抑制过早出现的终止密码子,诱导核糖体通读,不影响正常的终止密码子。为了评价该药物的安全性,本研究检测了PTC124对豚鼠心室肌细胞动作电位特性的急性效应。方法应用膜片钳方法研究PTC124对豚鼠心肌细胞动作电位的影响。采用酶法分离豚鼠心肌细胞,测定PTC124对心肌细胞的急性毒性作用。结果 PTC124对豚鼠心肌细胞静息膜电位、最大上升速率、动作电位幅度和动作电位持续时间在50和90%的复极期均没有受到影响。结论 PTC124不影响豚鼠心室肌细胞动作电位。该研究为今后评估这种疗法的使用价值,治疗具有潜在的致命性心律失常的BrS和/或传导障碍性疾病患者的安全性提供依据。Purpose Nonsense mutations that create premature termination codons （PTC） leading to disease by a mechanism of haploinsufficiency are relatively common in the SCNSA gene encoding the major sodium channel in heart. PTCs in SCN5A are associated with isolated conduction disease and Brugada syndrome （BrS）. Pharmacological therapy does not exist for these disorders, but would be highly beneficial. Recently, an orally bio-available drug capable of suppressing premature termination, PTC124, has been identified that selectively induces ribosomal read-through of premature but not normal termination codons. In this study, we tested the acute and long-term effects of PTC 124 on action potential characteristics of guinea pig ventricular cardiomyocytes. Methods The effects of PTC 124 on action potentials of isolated guinea pig ventricular eardiomyocytes were studied using the perforated patch-clamp methodology. Acute effects of PTC124 were measured in freshly isolated cardiomyocytes. Results Resting membrane potential, maximum upstroke velocity, action potential amplitude and action potential duration at 50 and 90% of repolarization were not affected by application of PTC 124. Conclusion PTC 124 has no acute effects on guinea pig ventricular action potentials. These experiments form the basis for future studies evaluating the use of this therapy in preventing potentially lethal arrhythmias in patients with BrS and/or conduction disease.

关 键 词：PTC124 心律失常 动作电位 心肌细胞 电生理特性 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]