Dissection of the voltage-activated potassium outward currents in adult mouse ventricular myocytes: I(to,f), I(to,s), I(K,slow1), I(K,slow2), and I(ss)

Jie Liu; Kyoung-Han Kim; Barry London; Michael J Morales; Peter H Backx

doi:10.1007/s00395-010-0134-z

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Dissection of the voltage-activated potassium outward currents in adult mouse ventricular myocytes: I(to,f), I(to,s), I(K,slow1), I(K,slow2), and I(ss)

Journal article

Peer reviewed

Dissection of the voltage-activated potassium outward currents in adult mouse ventricular myocytes: I(to,f), I(to,s), I(K,slow1), I(K,slow2), and I(ss)

Jie Liu, Kyoung-Han Kim, Barry London, Michael J Morales and Peter H Backx

Basic research in cardiology, Vol.106(2), pp.189-204

03/2011

DOI: 10.1007/s00395-010-0134-z

PMID: 21253754

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Abstract

Voltage-activated outward K(+) currents (I (Kv)) 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 I (Kv) in mouse myocardium have yielded inconsistencies. In this study, we developed a statistically rigorous method to uniquely quantify various I (Kv) 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 I (Kv) components. This method enabled us to reliably dissect the kinetic components of the decay phase of I (Kv) into fast (I (to)), intermediate (K(V)1.5-encoded I (K,slow1)) and slow (K(V)2-encoded I (K,slow2)) components. The most rapid kinetic phase, I (to), can be further dissected into fast (K(V)4-encoded I (to,f)) and slow (K(V)1.4-encoded I (to,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 K(V)1.1 transgene which largely abolished the 4-AP-sensitive portion of I (to) (i.e., I (to,s)) and the I (K,slow1) component. We also applied our method to Irx5-deficient mice and verified selective elevations of I (to) in endocardial myocytes. Our method should prove useful in future electrophysiological studies using mouse.

Potassium - metabolism

Patch-Clamp Techniques

Animals

Potassium Channels, Voltage-Gated - metabolism

Models, Cardiovascular

Mice, Inbred C57BL

Myocytes, Cardiac - metabolism

Male

Mice

Kinetics

Electrophysiologic Techniques, Cardiac

Mice, Knockout

Details

Title: Subtitle: Dissection of the voltage-activated potassium outward currents in adult mouse ventricular myocytes: I(to,f), I(to,s), I(K,slow1), I(K,slow2), and I(ss)
Creators: Jie Liu - Department of Physiology, University of Toronto, 150 College St., Toronto, ON M5S 3E2, Canada
Kyoung-Han Kim
Barry London
Michael J Morales
Peter H Backx
Resource Type: Journal article
Publication Details: Basic research in cardiology, Vol.106(2), pp.189-204
Publisher: Germany
DOI: 10.1007/s00395-010-0134-z
PMID: 21253754
ISSN: 0300-8428
eISSN: 1435-1803
Language: English
Date published: 03/2011
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984025572202771

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