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

线粒体功能障碍通过氧化磷酸化受损降低成肌细胞中KIR2.1 K(+)通道的活性。

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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 (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+)-activated 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.

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