Dissection of the voltage-activated potassium outward currents B in adult mouse ventricular myocytes: Ito,f, Ito,s, IK,slow1, IK,slow2, and Iss
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jie Liu Kyoung-Han Kim Barry London Michael J. Morales Peter H. Backx
- چاپ و سال / کشور: 2010
Description
Voltage-activated outward K? currents (IKv) are essential for cardiac repolarization and are major factors in the electrophysiological remodeling and arrhythmias seen in heart disease. Mouse models have been useful for understanding cardiac electrophysiology. However, previous methods for separating and quantifying the components of IKv in mouse myocardium have yielded inconsistencies. In this study, we developed a statistically rigorous method to uniquely quantify various IKv in adult mouse ventricular myocytes, and concluded that tri-exponential functions combined with depolarizing pulses of duration greater than 20 s are essential to adequately separate the different IKv components. This method enabled us to reliably dissect the kinetic components of the decay phase of IKv into fast (Ito), intermediate (KV1.5-encoded IK,slow1) and slow (KV2- encoded IK,slow2) components. The most rapid kinetic phase, Ito, can be further dissected into fast (KV4-encoded Ito,f) and slow (KV1.4-encoded Ito,s) components by measuring recovery from inactivation, voltage-dependence of activation and sensitivity to HpTx-2 and 4-AP. The applicability of our dissection method was validated using transgenic mice over-expressing dominant-negative KV1.1 transgene which largely abolished the 4-AP-sensitive portion of Ito (i.e., Ito,s) and the IK,slow1 component. We also applied our method to Irx5-deficient mice and verified selective elevations of Ito in endocardial myocytes. Our method should prove useful in future electrophysiological studies using mouse.
Basic Res Cardiol (2011) 106:189–204 Received: 9 July 2010 / Revised: 27 October 2010 / Accepted: 4 November 2010 / Published online: 21 January 2011
