IMR Press / FBL / Volume 28 / Issue 3 / DOI: 10.31083/j.fbl2803051
Open Access Original Research
The Effect of TWIK-1 Two Pore Potassium Channels on Cardiomyocytes in Low Extracellular Potassium Conditions
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1 National Traditional Chinese Medicine Clinical Research Base and Department of Cardiovascular Medicine of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
2 Institute of Integrated Chinese and Western Medicine, Southwest Medical University, 646000 Luzhou, Sichuan, China
3 Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, Sichuan, China
4 Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
5 Department of Orthodontics, Orofacial Reconstruction and Regeneration Laboratory, The Affiliated Stomatology Hospital of Southwest Medical University, 646000 Luzhou, Sichuan, China
*Correspondence: (Jin Zeng); (Dongchuan Zuo)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(3), 51;
Submitted: 31 August 2022 | Revised: 28 November 2022 | Accepted: 19 December 2022 | Published: 15 March 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Backgroound: At low extracellular potassium ([K+]e) conditions, human cardiomyocytes can depolarize to –40 mV. This is closely related to hypokalemia-induced fatal cardiac arrhythmia. The underlying mechanism, however, is still not well understood. TWIK-1 channels are background K+ channels that are highly expressed in human cardiomyocytes. We previously reported that TWIK-1 channels changed ion selectivity and conducted leak Na+ currents at low [K+]e. Moreover, a specific threonine residue (Thr118) within the ion selectivity filter was responsible for this altered ion selectivity. Methods: Patch clamp were used to investigate the effects of TWIK-1 channels on the membrane potentials of cardiomyocytes in response to low [K+]e. Results: At 2.7 mM [K+]e and 1 mM [K+]e, both Chinese hamster ovary (CHO) cells and HL-1 cells ectopically expressed human TWIK-1 channels displayed inward leak Na+ currents and reconstitute depolarization of membrane potential. In contrast, cells ectopically expressed human TWIK-1-T118I mutant channels that remain high selectivity to K+ exhibited hyperpolarization of membrane potential. Furthermore, human iPSC-derived cardiomyocytes showed depolarization of membrane potential in response to 1 mM [K+]e, while the knockdown of TWIK-1 expression eliminated this phenomenon. Conclusions: These results demonstrate that leak Na+ currents conducted by TWIK-1 channels contribute to the depolarization of membrane potential induced by low [K+]e in human cardiomyocytes.

membrane potential depolarization
TWIK-1 channels
81800303/National Natural Science Foundation of China
2019LZXNYDJ01/Luzhou-Southwest Medical University Joint Project
2020LZXNYDJ05/Luzhou-Southwest Medical University Joint Project
[2020]33/National TCM Clinical Research Base construction unit scientific research project (the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
2021ZD015/Major project of Sichuan Provincial Administration of Traditional Chinese Medicine
2022YFS0618/Science and Technology Department of Sichuan Province
Fig. 1.
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