The KATP channel is a molecular sensor of atrophy in skeletal muscle

Domenico Tricarico*, Antonietta Mele, Giulia Maria Camerino, Roberto Bottinelli, Lorenza Brocca, Antonio Frigeri, Maria Svelto, Alfred L. George, Diana Conte Camerino

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The involvement of ATP-sensitive K+ (KATP) channels in the atrophy of slow-twitch (MHC-I) soleus (SOL) and fast-twitch (MHC-IIa) flexor digitorum brevis (FDB) muscles was investigated in vivo in 14-day-hindlimb-unloaded (14-HU) rats, an animal model of disuse, and in vitro in drug-induced muscle atrophy. Patch-clamp and gene expression experiments were performed in combination with measurements of fibre diameters used as an index of atrophy, and with MHC labelling in 14-HU rats and controls. A down-regulation of KATP channel subunits Kir6.2, SUR1 and SUR2B with marked atrophy and incomplete phenotype transition were observed in SOL of 14-HU rats. The observed changes in KATP currents were well correlated with changes in fibre diameters and SUR1 expression, as well as with MHC-IIa expression. Half of the SOL fibres of 14-HU rats had reduced diameter and KATP currents and were labelled by MHC-I antibodies. Non-atrophic fibres were labelled by MHC-IIa (22%) antibodies and had enhanced KATP currents, or were labelled by MHC-I (28%) antibodies but had normal current. FDB was not affected in 14-HU rats and this is related to the high expression/activity of Kir6.2/SUR1 subunits characterizing this muscle phenotype. The long-term incubation of the control muscles in vitro with the KATP channel blocker glibenclamide (10-6 m) reduced the KATP currents with atrophy and these effects were prevented by the KATP channel opener diazoxide (10-4 m). The in vivo down-regulation of SUR1, and possibly of Kir6.2 and SUR2B, or their in vitro pharmacological blockade activates atrophic signalling in skeletal muscle. All these findings suggest a new role for the KATP channel as a molecular sensor of atrophy.

Original languageEnglish (US)
Pages (from-to)773-784
Number of pages12
JournalJournal of Physiology
Issue number5
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Physiology


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