PubMed 24998494

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir6.2 , Slo1

Title: Dual response of the KATP channels to staurosporine: a novel role of SUR2B, SUR1 and Kir6.2 subunits in the regulation of the atrophy in different skeletal muscle phenotypes.

Authors: Antonietta Mele, Giulia M Camerino, Sara Calzolaro, Maria Cannone, Diana Conte, Domenico Tricarico

Journal, date & volume: Biochem. Pharmacol., 2014 Sep 15 , 91, 266-75

PubMed link:

We investigated on the role of the genes encoding for the ATP-sensitive K(+)-channel (KATP) subunits (SUR1-2A/B, Kir6.2) in the atrophy induced "in vitro" by staurosporine (STS) in different skeletal muscle phenotypes of mouse. Patch-clamp and gene expression experiments showed that the expression/activity of the sarcolemma KATP channel subunits was higher in the fast-twitch than in the slow-twitch fibers. After 1 to 3h of incubation time, the STS (2.14×10(-6)M) treatment enhanced the expression/activity of the SUR2B, SUR1 and Kir6.2 subunit genes, but not SUR2A, in the slow-twitch muscle fibers, induced the caspase-3-9, Atrogin-1 and Murf-1 gene expression without affecting protein content. After 3 to 6h, the STS-related atrophy markedly down-regulated the SUR2B, SUR1 and Kir6.2 genes reducing the KATP currents and reduced the protein content/muscle weight ratio of the slow-twitch muscle by -36.4±6% (p<0.05). After 6 to 24h, no additional changes of the SUR1-2B and Kir6.2 gene expression and muscle protein were observed. In the fast-twitch muscles, STS mildly affected the atrophic genes and protein content, but potentiated the KATP currents down-regulating the Bnip-3 gene. Diazoxide (250-500×10(-6)M), a SUR1-2B/Kir6.2 channel opener, prevented the protein loss induced by STS in the slow-twitch muscle after 6h showing an EC50 of 1.35×10(-7)M and Emax of 75%, down-regulated the caspase-9 gene and enhanced the KATP currents. The enhanced expression/activity of the SUR2B, SUR1 and Kir6.2 genes are cytoprotective against STS-induced atrophy in the slow-twitch muscle; their reduced expression/activity is associated with proteolysis and atrophy in skeletal muscle.