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K2p3.1 protein is expressed as a transmural gradient across the rat left ventricular free wall

Jones, Sandra A.; Walton, Richard D.; Morton, Michael; Lancaster, Matthew K.

Authors

Richard D. Walton

Michael Morton

Matthew K. Lancaster



Abstract

Introduction: K 2p 3.1, also known as TASK-1, is a twin-pore acid-sensitive repolarizing K + channel, responsible for a background potassium current that significantly contributes to setting the resting membrane potential of cardiac myocytes. Inhibition of I K2p3.1 alters cardiac repolarization and is proarrhythmogenic. In this study, we have examined the expression of K 2p 3.1 and function of this channel in tissue and myocytes from across the left ventricular free wall. Methods and Results: Using fluorescence immunocytochemistry, the expression of K 2p 3.1 protein in myocytes from the subendocardial region was found to be twice (205% ± 13.5%) that found in myocytes from the subepicardial region of the left ventricle (100% ± 5.3%). The left ventricular free wall exhibited a marked transmural gradient of K 2p 3.1 protein expression. Western blot analysis confirmed significantly higher K 2p 3.1 protein expression in subendocardial tissue (156% ± 2.5%) than subepicardial tissue (100% ± 5.0%). However, there was no difference in K 2p 3.1 messenger RNA expression. Whole-cell patch clamp identified I K2p3.1 current density to be significantly greater in myocytes isolated from the subendocardium (7.66 ± 0.53 pA/pF) compared with those from the subepicardium (3.47 ± 0.74 pA/pF). Conclusions: This is the first study to identify a transmural gradient of K 2p 3.1 in the left ventricle. This gradient has implications for understanding ventricular arrhythmogenesis under conditions of ischemia but also in response to other modulatory factors, such as adrenergic stimulation and the presence of anesthetics that inhibits or activates this channel.

Citation

Jones, S. A., Walton, R. D., Morton, M., & Lancaster, M. K. (2019). K2p3.1 protein is expressed as a transmural gradient across the rat left ventricular free wall. Journal of Cardiovascular Electrophysiology, 30(3), 383-391. https://doi.org/10.1111/jce.13805

Journal Article Type Article
Acceptance Date Nov 15, 2018
Online Publication Date Dec 28, 2018
Publication Date Mar 1, 2019
Deposit Date Nov 19, 2018
Publicly Available Date Oct 27, 2022
Journal Journal of Cardiovascular Electrophysiology
Print ISSN 1045-3873
Electronic ISSN 1540-8167
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 30
Issue 3
Pages 383-391
DOI https://doi.org/10.1111/jce.13805
Keywords K2p3.1; TASK-1; Ventricular; Heterogeneity; Repolarisation; Electrophysiology
Public URL https://hull-repository.worktribe.com/output/1155208
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1111/jce.13805
Additional Information Published in Journal of Cardiovascular Electrophysiology

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Copyright Statement
© 2018 The Authors

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.







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