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


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

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


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