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

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

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 DNAdepleted (ρ0) L6 myoblasts. The ρ0 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₊-ctivated K₊ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the I_Kir. The ρ0 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 ρ0 myoblasts.