| First Author | King EC | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 7 | Pages | 2937-2947 |
| PubMed ID | 28356343 | Mgi Jnum | J:247843 |
| Mgi Id | MGI:5925487 | Doi | 10.1096/fj.201600965RR |
| Citation | King EC, et al. (2017) Targeted deletion of Kcne3 impairs skeletal muscle function in mice. FASEB J 31(7):2937-2947 |
| abstractText | KCNE3 (MiRP2) forms heteromeric voltage-gated K+ channels with the skeletal muscle-expressed KCNC4 (Kv3.4) alpha 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 alpha subunit remodeling arising from Kcne3 deletion was highly specific, involving just 3 of 69 alpha 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 force with repetitive stimuli of hind-limb muscle, both in vivo and in vitro, this was absent in 6 of 6 Kcne3-/- mice tested. Finally, myoblasts isolated from Kcne3-/- mice exhibit faster-inactivating and smaller sustained outward currents than those from Kcne3+/+ mice. Thus, Kcne3 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 Kcne3 impairs skeletal muscle function in mice. |
