Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.
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 +/- 9 pS (n=5) and a density of expression comparable to that seen in excitable cells.


CONCLUSIONS
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.
Mobasheri
A
A
Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK.
Gent
T C
TC
Nash
A I
AI
Womack
M D
MD
Moskaluk
C A
CA
Barrett-Jolley
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D006736:Horses; D006801:Humans; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000502:physiology; D010003:Osteoarthritis / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism* / Q000502:physiology; D000099161:Kcnj11 Channel
D000255:Adenosine Triphosphate; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel