Evidence for functional ATP-sensitive (KATP) potassium channels in human and equine articular chondrocytes

Mobasheri, A.; Gent, T.C.; Nash, A.I.; Womack, M.D.; Moskaluk, C.A.; Barrett-Jolley, R.

doi:10.1016/j.joca.2006.06.017

Next »Osteoarthritis and Cartilage
Volume 15, Issue 1 , Pages 1-8, January 2007

Evidence for functional ATP-sensitive (K_ATP) potassium channels in human and equine articular chondrocytes

A. Mobasheri, B.Sc., A.R.C.S. (Hons.), M.Sc., D.Phil. (Oxon.) (Associate Professor)
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK
- Division of Comparative Medicine, The School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK
T.C. Gent, B.Sc. (Hons.) (Research Student)
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK
A.I. Nash, B.Sc. (Hons.) (Undergraduate Student)
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK
M.D. Womack, B.Sc. (Hons.), Ph.D. (Hons.) (Research Fellow)
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK
C.A. Moskaluk, M.D., Ph.D. (Associate Professor)
- Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908, United States of America
- Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908, United States of America
R. Barrett-Jolley, B.Sc. (Hons.), D.Phil. (Oxon.) (Lecturer)
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK
- Address for correspondence and reprint requests to: Richard Barrett-Jolley, B.Sc. (Hons.), D.Phil. (Oxon.), Lecturer, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK. Tel: 44-151-794-4225; Fax: 44-151-794-4243.

Received 15 December 2005; accepted 25 June 2006.

Summary

Objective

Chondrocytes are highly sensitive to variations in extracellular glucose and oxygen levels in the extracellular matrix. As such, they must possess a number of mechanisms to detect and respond to alterations in the metabolic state of cartilage. In other organs such as the pancreas, heart and brain, such detection is partly mediated by a family of potassium channels known as K_ATP (adenosine 5′-triphosphate-sensitive potassium) channels. Here we investigate whether chondrocytes too express functional K_ATP channels, which might, potentially, serve to couple metabolic state with cell activity.

Methods

Immunohistochemistry was used to explore K_ATP channel expression in equine and human chondrocytes. Biophysical properties of equine chondrocyte K_ATP channels were investigated with patch-clamp electrophysiology.

Results

Polyclonal antibodies directed against the K_ATP Kir6.1 subunit revealed high levels of expression in human and equine chondrocytes mainly in superficial and middle zones of normal cartilage. Kir6.1 was also detected in superficial chondrocytes in osteoarthritic (OA) cartilage. In single-channel electrophysiological studies of equine chondrocytes, we found K_ATP channels to have a maximum unitary conductance of 47±9pS (n=5) and a density of expression comparable to that seen in excitable cells.

Conclusion

We have shown, for the first time, functional K_ATP channels in chondrocytes. This suggests that K_ATP channels are involved in coupling metabolic and electrical activities in chondrocytes through sensing of extracellular glucose and intracellular adenosine triphosphate (ATP) levels. Altered K_ATP channel expression in OA chondrocytes may result in impaired intracellular ATP sensing and optimal metabolic regulation.

Key words: Cartilage, Osteoarthritis, Chondrocyte, ATP-sensitive potassium channel, K_ATP, Kir6.1, Ion channel, Immunohistochemistry