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

Myoblast fusion depends on mitochondrial integrity and intracellular Ca2+ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with [Ca2+ ]i regulation in normal and mitochondrial DNA-depleted (ρ0) L6 myoblasts. The ρ0 myoblasts showed impaired myotube formation. The inwardly rectifying K+ current (IKir ) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated Ca2+ channel and Ca2+ -activated K+ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the IKir . The ρ0 myoblasts showed depolarized resting membrane potential and higher basal [Ca2+ ]i . Our results demonstrated the specific downregulation of IKir by dysfunctional mitochondria. The resultant depolarization and altered Ca2+ signaling might be associated with impaired myoblast fusion in ρ0 myoblasts.