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

• Published in: The Korean journal of physiology & pharmacology 2018-11, Vol.22 (6), p.697-703
• Main Authors: Woo, JooHan, Kim, Hyun Jong, Nam, Yu Ran, Kim, Yung Kyu, Lee, Eun Ju, Choi, Inho, Kim, Sung Joon, Lee, Wan, Nam, Joo Hyun
• Format: Article
• Language: Korean
• ISSN: 1226-4512; 2093-3827

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.