The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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)
  • Received : 2018.07.16
  • Accepted : 2018.08.29
  • Published : 2018.11.01
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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.

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