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Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing

Rufino, Ana T.; Rosa, Susana C.; Judas, Fernando; Mobasheri, Ali; Lopes, M. Celeste; Mendes, Alexandrina F.

Authors

Ana T. Rufino

Susana C. Rosa

Fernando Judas

Ali Mobasheri ali.mobasheri@nottingham.ac.uk

M. Celeste Lopes

Alexandrina F. Mendes afmendes@ff.uc.pt



Abstract

ATP-sensitive potassium [K(ATP)] channels sense intracellular ATP/ADP levels, being essential components of a glucose-sensing apparatus in various cells that couples glucose metabolism, intracellular ATP/ADP levels and membrane potential. These channels are present in human chondrocytes, but their subunit composition and functions are unknown. This study aimed at elucidating the subunit composition of K(ATP) channels expressed in human chondrocytes and determining whether they play a role in regulating the abundance of major glucose transporters, GLUT-1 and GLUT-3, and glucose transport capacity. The results obtained show that human chondrocytes express the pore forming subunits, Kir6.1 and Kir6.2, at the mRNA and protein levels and the regulatory sulfonylurea receptor (SUR) subunits, SUR2A and SUR2B, but not SUR1. The expression of these subunits was no affected by culture under hyperglycemia-like conditions. Functional impairment of the channel activity, using a SUR blocker (glibenclamide 10 or 20 nM), reduced the protein levels of GLUT-1 and GLUT-3 by approximately 30% in normal chondrocytes, while in cells from cartilage with increasing osteoarthritic (OA) grade no changes were observed. Glucose transport capacity, however, was not affected in normal or OA chondrocytes. These results show that K(ATP) channel activity regulates the abundance of GLUT-1 and GLUT-3, although other mechanisms are involved in regulating the overall glucose transport capacity of human chondrocytes. Therefore, K(ATP) channels are potential components of a broad glucose sensing apparatus that modulates glucose transporters and allows human chondrocytes to adjust to varying extracellular glucose concentrations. This function of K(ATP) channels seems to be impaired in OA chondrocytes.

Citation

Rufino, A. T., Rosa, S. C., Judas, F., Mobasheri, A., Lopes, M. C., & Mendes, A. F. (2013). Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing. Journal of Cellular Biochemistry, 114(8), doi:10.1002/jcb.24532

Journal Article Type Article
Publication Date Aug 1, 2013
Deposit Date Apr 10, 2014
Publicly Available Date Apr 10, 2014
Journal Journal of Cellular Biochemistry
Print ISSN 0730-2312
Electronic ISSN 0730-2312
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 114
Issue 8
DOI https://doi.org/10.1002/jcb.24532
Public URL http://eprints.nottingham.ac.uk/id/eprint/2931
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/jcb.24532/full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0





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