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

SummaryObjectiveChondrocytes 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 KATP (adenosine 5′-triphosphate-sensitive potassium) channels. Here we investigate whether chondrocytes too express functional KATP channels, which might, potentially, serve to couple metabolic state with cell activity.MethodsImmunohistochemistry was used to explore KATP channel expression in equine and human chondrocytes. Biophysical properties of equine chondrocyte KATP channels were investigated with patch-clamp electrophysiology.ResultsPolyclonal antibodies directed against the KATP 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 KATP channels to have a maximum unitary conductance of 47±9pS (n=5) and a density of expression comparable to that seen in excitable cells.ConclusionWe have shown, for the first time, functional KATP channels in chondrocytes. This suggests that KATP channels are involved in coupling metabolic and electrical activities in chondrocytes through sensing of extracellular glucose and intracellular adenosine triphosphate (ATP) levels. Altered KATP channel expression in OA chondrocytes may result in impaired intracellular ATP sensing and optimal metabolic regulation