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http://dx.doi.org/10.4196/kjpp.2018.22.6.697

Mitochondrial dysfunction reduces the activity of KIR2.1 K+ channel in myoblasts via impaired oxidative phosphorylation  

Woo, JooHan (Department of Biomedical Sciences, Seoul National University College of Medicine)
Kim, Hyun Jong (Department of Physiology, Dongguk University College of Medicine)
Nam, Yu Ran (Department of Physiology, Dongguk University College of Medicine)
Kim, Yung Kyu (Department of Physiology, Dongguk University College of Medicine)
Lee, Eun Ju (Department of Medical Biotechnology, Yeungnam University)
Choi, Inho (Department of Medical Biotechnology, Yeungnam University)
Kim, Sung Joon (Department of Biomedical Sciences, Seoul National University College of Medicine)
Lee, Wan (Channelopathy Research Center (CRC), Dongguk University College of Medicine)
Nam, Joo Hyun (Department of Physiology, Dongguk University College of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.22, no.6, 2018 , pp. 697-703 More about this Journal
Abstract
Myoblast fusion depends on mitochondrial integrity and intracellular $Ca^{2+}$ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with $[Ca^{2+}]_i$ regulation in normal and mitochondrial DNA-depleted(${\rho}0$) L6 myoblasts. The ${\rho}0$ myoblasts showed impaired myotube formation. The inwardly rectifying $K^+$ current ($I_{Kir}$) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated $Ca^{2+}$ channel and $Ca^{2+}$-activated $K^+$ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the $I_{Kir}$. The ${\rho}0$ myoblasts showed depolarized resting membrane potential and higher basal $[Ca^{2+}]_i$. Our results demonstrated the specific downregulation of $I_{Kir}$ by dysfunctional mitochondria. The resultant depolarization and altered $Ca^{2+}$ signaling might be associated with impaired myoblast fusion in ${\rho}0$ myoblasts.
Keywords
Inward-rectifying $K^+$ channel; MtDNA-depleted myoblasts; Myoblast; Myogenesis; Oxidative phosphorylation;
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