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

Research output: Contribution to journalArticle

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Abstract

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
Pages (from-to)773-784
Number of pages12
JournalJournal of Physiology
Volume588
Issue number5
DOIs
Publication statusPublished - Mar 2010

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KATP Channels
Hindlimb
Atrophy
Skeletal Muscle
Muscles
Antibodies
Down-Regulation
Phenotype
Diazoxide
Muscular Atrophy
Glyburide
Animal Models
Adenosine Triphosphate
Pharmacology
Gene Expression
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

Cite this

Tricarico, D., Mele, A., Camerino, G. M., Bottinelli, R., Brocca, L., Frigeri, A., ... Camerino, D. C. (2010). The KATP channel is a molecular sensor of atrophy in skeletal muscle. Journal of Physiology, 588(5), 773-784. https://doi.org/10.1113/jphysiol.2009.185835

The KATP channel is a molecular sensor of atrophy in skeletal muscle. / Tricarico, Domenico; Mele, Antonietta; Camerino, Giulia Maria; Bottinelli, Roberto; Brocca, Lorenza; Frigeri, Antonio; Svelto, Maria; George, Alfred L.; Camerino, Diana Conte.

In: Journal of Physiology, Vol. 588, No. 5, 03.2010, p. 773-784.

Research output: Contribution to journalArticle

Tricarico, D, Mele, A, Camerino, GM, Bottinelli, R, Brocca, L, Frigeri, A, Svelto, M, George, AL & Camerino, DC 2010, 'The KATP channel is a molecular sensor of atrophy in skeletal muscle', Journal of Physiology, vol. 588, no. 5, pp. 773-784. https://doi.org/10.1113/jphysiol.2009.185835
Tricarico, Domenico ; Mele, Antonietta ; Camerino, Giulia Maria ; Bottinelli, Roberto ; Brocca, Lorenza ; Frigeri, Antonio ; Svelto, Maria ; George, Alfred L. ; Camerino, Diana Conte. / The KATP channel is a molecular sensor of atrophy in skeletal muscle. In: Journal of Physiology. 2010 ; Vol. 588, No. 5. pp. 773-784.
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