Manipulation of KCNE2 expression modulates action potential duration and Ito and IK in rat and mouse ventricular myocytes.
In heterologous expression systems, KCNE2 has been demonstrated to interact with multiple α-subunits of voltage-dependent cation channels and modulate their functions. However, the physiological and pathological roles of KCNE2 in cardiomyocytes are poorly understood. The present study aimed to investigate the effects of bidirectional modulation of KCNE2 expression on action potential (AP) duration (APD) and voltage-dependent K(+) channels in cardiomyocytes. Adenoviral gene delivery and RNA interference were used to either increase or decrease KCNE2 expression in cultured neonatal and adult rat or neonatal mouse ventricular myocytes. Knockdown of KCNE2 prolonged APD in both neonatal and adult myocytes, whereas overexpression of KCNE2 shortened APD in neonatal but not adult myocytes. Consistent with the alterations in APD, KCNE2 knockdown decreased transient outward K(+) current (Ito) densities in neonatal and adult myocytes, whereas KCNE2 overexpression increased Ito densities in neonatal but not adult myocytes. Furthermore, KCNE2 knockdown accelerated the rates of Ito activation and inactivation, whereas KCNE2 overexpression slowed Ito gating kinetics in neonatal but not adult myocytes. Delayed rectifier K(+) current densities were remarkably affected by manipulation of KCNE2 expression in mouse but not rat cardiomyocytes. Simulation of the AP of a rat ventricular myocyte with a mathematical model showed that alterations in Ito densities and gating properties can result in similar APD alterations in KCNE2 overexpression and knockdown cells. In conclusion, endogenous KCNE2 in cardiomyocytes is important in maintaining cardiac electrical stability mainly by regulating Ito and APD. Perturbation of KCNE2 expression may predispose the heart to ventricular arrhythmia by prolonging APD.
['Liu|Wen-juan|WJ|', 'Deng|Jian-xin|JX|', 'Wang|Gang|G|', 'Gao|Kai-ping|KP|', 'Lin|Ze-xun|ZX|', 'Liu|Shuai-ye|SY|', 'Wang|Yong-hui|YH|', 'Liu|Jie|J|']
D000200:Action Potentials D000256:Adenoviridae D000367:Age Factors D000818:Animals D000831:Animals, Newborn D002478:Cells, Cultured D005786:Gene Expression Regulation D055785:Gene Knockdown Techniques D005822:Genetic Vectors D006352:Heart Ventricles D015640:Ion Channel Gating D007700:Kinetics D008810:Mice, Inbred C57BL D032383:Myocytes, Cardiac D011188:Potassium D024642:Potassium Channels, Voltage-Gated D034622:RNA Interference D017207:Rats, Sprague-Dawley D014162:Transfection
KCNE2 action potential cardiomyocytes delayed rectifier K+ current transient outward K+ current