KCNC4

Potassium voltage-gated channel subfamily C member 4 (KSHIIIC) (Voltage-gated potassium channel subunit Kv3.4) [C1orf30]

Publications

Targeted deletion of [i]Kcne3[/i] impairs skeletal muscle function in mice.

PubMed

Full text

KCNE3 (MiRP2) forms heteromeric voltage-gated K channels with the skeletal muscle-expressed KCNC4 (K 3.4) α subunit. [i]KCNE3[/i] was the first reported skeletal muscle K channel disease gene, but the requirement for [i]KCNE3[/i] in skeletal muscle has been questioned. Here, we confirmed KCNE3 transcript and protein expression in mouse skeletal muscle using [i]Kcne3[/i] tissue as a negative control. Whole-transcript microarray analysis (770,317 probes, interrogating 28,853 transcripts) findings were consistent with [i]Kcne3[/i] deletion increasing gastrocnemius oxidative metabolic gene expression and the proportion of type IIa fast-twitch oxidative muscle fibers, which was verified using immunofluorescence. The down-regulated transcript set overlapped with muscle unloading gene expression profiles (≥1.5-fold change; [i]P[/i] < 0.05). Gastrocnemius K channel α subunit remodeling arising from [i]Kcne3[/i] deletion was highly specific, involving just 3 of 69 α subunit genes probed: known KCNE3 partners KCNC4 and KCNH2 (mERG) were down-regulated, and KCNK4 (TRAAK) was up-regulated ([i]P[/i] < 0.05). Functionally, [i]Kcne3[/i] mice exhibited abnormal hind-limb clasping upon tail suspension (63% of [i]Kcne3[/i] mice ≥10-mo-old [i]vs.[/i] 0% age-matched [i]Kcne3[/i] littermates). Whereas 5 of 5 [i]Kcne3[/i] mice exhibited the typical biphasic decline in contractile force with repetitive stimuli of hind-limb muscle, both [i]in vivo[/i] and [i]in vitro,[/i] this was absent in 6 of 6 [i]Kcne3[/i] mice tested. Finally, myoblasts isolated from [i]Kcne3[/i] mice exhibit faster-inactivating and smaller sustained outward currents than those from [i]Kcne3[/i] mice. Thus, [i]Kcne3[/i] deletion impairs skeletal muscle function in mice.-King, E. C., Patel, V., Anand, M., Zhao, X., Crump, S. M., Hu, Z., Weisleder, N., Abbott, G. W. Targeted deletion of [i]Kcne3[/i] impairs skeletal muscle function in mice.

MeSH Terms

• Aging
• Animals
• Down-Regulation
• Female
• Gene Expression Regulation
• Mice
• Mice, Knockout
• Muscle Contraction
• Muscle, Skeletal
• Myoblasts
• Potassium Channels, Voltage-Gated
• Protein Array Analysis
• Transcriptome
• Up-Regulation

Keywords

• Kv3.4
• MiRP2
• myotonia
• periodic paralysis
• potassium channel