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.
abstract: 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.
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: antonietta.mele@uniba.it.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Mele
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: giuliamaria.camerino@uniba.it.
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Camerino
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: sara.calzolaro@uniba.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Calzolaro
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: mariacannone@libero.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Cannone
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: diana.conte@uniba.it.
authors.forename: Diana
authors.initials: D
authors.lastname: Conte
authors.affiliation: Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona n 4, 70125 Bari, Italy. Electronic address: domenico.tricarico@uniba.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricarico
mesh_terms: D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism*; D000099161:Kcnj11 Channel
chemical_list: D003981:Diazoxide; D004791:Enzyme Inhibitors; D024661:Potassium Channels, Inwardly Rectifying; D019311:Staurosporine; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577508:Abcc8 protein, mouse; C577511:Abcc9 protein, mouse
keywords: Apoptosis; Atrophy; Autophagy; Diazoxide; KATP channel subunits; Skeletal muscle