细胞外液低钾对小鼠心室肌细胞跨膜电位影响的定量分析
投稿时间:2015-06-11  修订日期:2015-06-12  点此下载全文
引用本文:杨素雨,高倩,闫莉,谷婧丽,郝维,曹济民.细胞外液低钾对小鼠心室肌细胞跨膜电位影响的定量分析[J].医学研究杂志,2016,45(1):19-24
DOI: 10.11969/j.issn.1673-548X.2016.01.006
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作者单位E-mail
杨素雨 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系  
高倩 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系  
闫莉 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系  
谷婧丽 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系  
郝维 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系  
曹济民 100005 北京, 中国医学科学院基础医学研究所/北京协和医学院基础学院生理学系 caojimin@126.com 
基金项目:国家自然科学基金资助项目(31171088)
中文摘要:目的 研究不同程度细胞外低钾对心肌细胞跨膜电位的效应,阐明低钾对心肌细胞电生理特性的详细影响。方法 分离C57BL/6J小鼠的左心室乳头肌,采用标准玻璃微电极胞内记录技术记录心室肌细胞的跨膜电位,观察细胞外液K+浓度由正常的5.4mmol/L分别降为3、2、1和0mmol/L时,心室肌细胞跨膜电位各参数的变化。结果 低钾对心肌细胞的静息电位(RP)有双向影响:细胞外K+浓度降为3mmol/L时,RP显著增大(超极化)(P=0.000),而细胞外K+浓度降为2、1和0mmol/L时,细胞RP先显著增大后显著减小(P=0.000),这些结果异于传统观点。当细胞外液K+浓度为3mmol/L时,动作电位振幅(APA)和0期最大除极速度(Vmax)均增大,动作电位时程APD10、APD20、APD50和APD90均显著缩短(P<0.05),而动作电位复极到APD90后,复极速度减慢,即复极化有拖尾现象。当细胞外K+浓度为2mmol/L时,APA极度减小,Vmax明显减慢,AP呈侏儒型,而当细胞外K+浓度为1和0mmol/L时,细胞兴奋性丧失,电刺激不能诱发动作电位。此外,低钾可诱发早期后除极以及连串的触发活动,且后者两种形式,也表现为量-效和时-效的特点。结论 细胞外液低钾对心室肌细胞的RP、APA和Vmax有双重影响:中度低钾(K+ 3mmol/L)使这3个参数均增大;重度低钾(K+ 2mmol/L及以下)使这3个参数均减小;低钾使动作电位早期复极加快,晚期复极减慢;极度低钾(K+ 1mmol/L及以下)会导致心室肌细胞的兴奋性丧失;中、重度低钾可导致心室肌细胞发生早期后除极及连串的触发活动,后者相当于细胞水平的心动过速,但不是工作细胞获得了自律性。本研究在一定程度上澄清了以往对低钾的心肌电生理效应的模糊认识。
中文关键词:低血钾  心肌细胞  静息电位  动作电位  触发活动
 
Quantitative Analysis of the Effects of Hypokalemia on the Transmembrane Potential of Mice Cardiomyocytes
Abstract:Objective To investigate the effects of hypokalemia on the transmembrane potentials of cardiomyocytes, aiming to clarify ambiguous understandings and the detailed effects of hypokalemia on myocardial electrophysiology. Methods Isolated left ventricular papillary muscles of C57BL/6J mice were used as a model. The transmembrane potentials of ventricular myocytes were recorded intracellularly using the standard microelectrode technique, and extracellular K+ concentrations (in mmol/L) were set at 5.4 to 3, 2, 1 and 0. Results Low extracellular potassium showed bidirectional effects on the resting potential (RP):RP increased significantly when extracellular K+ concentration was reduced to 3 mmol/L (P=0.000), RP increased first and then decreased when extracellular K+ concentrations was reduced to 2, 1, and 0 mmol/L (P=0.000). Three mmol/L extracellular K+ increased the action potential amplitude (APA) and the maximal depolarization velocity (Vmax), and shortened the action potential duration (APD) at APD10, APD20, APD50 and APD90, but prolonged the overall APD mainly due to a longer APD tail (APD90-APD100). APA and Vmax decreased dramatically, and the AP shape became a 'pygmy' type configuration when extracellular K+ concentration was at 2 mmol/L. The excitability of cardiomyocytes diminished when extracellular K+ concentrations was at 1 or 0 mmol/L. In addition, early afterdepolarization and triggered activities with two configurations were observed during low extracellular K+ and also showed dose-response and time-response relationships. Conclusion Extracellular low potassium has bidirectional effects on the RP,APA and Vmax of ventricular myocytes. Mild low potassium (K+ 3 mmol/L) increases the values of above three parameters, but severe low potassium (K+ 2 mmol/L or lower) decreases the three parameters. Low potassium accelerates early repolarization of action potential but slows down late repolarization. Extream low potassium (K+ 1 mmol/L or lower) abolishes cell excitability. Moderate to severe low potassium may induce early afterdepolarization and consecutive triggered activities. The latter is likely the tachycardia at the cellular level, but does not mean that working cardiomyocytes have acquired autorhythmicity. The study clarifies some ambiguous understandings on the electrophysiological effects of hypokalemia on cardiomyocytes.
keywords:Hypokalemia  Cardiomyocytes  Resting potential  Action potential  Triggered activity
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