Title Targeted deletion of Kcne 3 impairs skeletal muscle function in mice Permalink

Content Provider	Semantic Scholar
Author	King, Elizabeth C. Patel, Vishal Anand, Marie Zhao, Xiaoli Crump, Shawn M. Hu, Zhaoyang Weisleder, Noah L. Abbott, Geoffrey W.
Copyright Year	2017
Abstract	KCNE3 (MiRP2) forms heteromeric voltage-gated K channels with the skeletal muscle-expressed KCNC4 (Kv3.4) a subunit. KCNE3 was the first reported skeletal muscle K + channel disease gene, but the requirement for KCNE3 in skeletal muscle has been questioned. Here, we confirmed KCNE3 transcript and protein expression in mouse skeletal muscle using Kcne3 tissue as a negative control. Whole-transcript microarray analysis (770,317 probes, interrogating 28,853 transcripts) findings were consistent with Kcne3 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; P < 0.05). Gastrocnemius K channel a subunit remodeling arising from Kcne3 deletion was highly specific, involving just 3 of 69 a subunit genes probed: known KCNE3 partners KCNC4 and KCNH2 (mERG) were down-regulated, and KCNK4 (TRAAK) was up-regulated (P < 0.05). Functionally, Kcne3 mice exhibited abnormal hind-limb clasping upon tail suspension (63% of Kcne3 mice ‡10-mo-old vs. 0% age-matched Kcne3 littermates). Whereas 5 of 5 Kcne3 mice exhibited the typical biphasic decline in contractile forcewith repetitive stimuli of hind-limbmuscle, both in vivo and in vitro, thiswas absent in 6 of 6 Kcne3 mice tested. Finally, myoblasts isolated from Kcne3 mice exhibit faster-inactivating and smaller sustainedoutward currents than those fromKcne3mice. Thus,Kcne3deletion impairs skeletalmuscle 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 Kcne3 impairs skeletal muscle function in mice. FASEB J. 31, 2937–2947 (2017). www.fasebj.org
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://cloudfront.escholarship.org/dist/prd/content/qt32n8d394/qt32n8d394.pdf?t=ou2n4m
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article