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

Abstract：

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. 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.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Mobasheri A,Gent TC,Nash AI,Womack MD,Moskaluk CA,Barrett-Jolley R

doi

10.1016/j.joca.2006.06.017

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

1-8

issue

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(06)00205-6

journal_volume

pub_type

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