Evidence for functional ATP-sensitive (KATP) potassium channels in human and equine articular chondrocytes
Evidence for functional ATP-sensitive (KATP) potassium channels in human and equine articular chondrocytes
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DOI：
10.1016/j.joca.2006.06.017
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发表时间：
2007-01-01
影响因子：
7
通讯作者：
Barrett-Jolley, R.
中科院分区：
文献类型：
--
作者：
Mobasheri, A.;Gent, T. C.;Barrett-Jolley, R.
目的：软骨细胞对细胞外基质中细胞外葡萄糖和氧水平的变化高度敏感。因此，它们必须具有许多机制来检测和响应软骨代谢状态的变化。在胰腺、心脏和大脑等其他器官中，这种检测部分是由K-ATP（腺苷5′-三磷酸敏感钾）通道家族介导的。在这里，我们研究软骨细胞是否也表达功能性K-ATP通道，这可能潜在地将代谢状态与细胞活性偶联。方法：采用免疫组织化学方法观察K-ATP通道在马和人软骨细胞中的表达。采用膜片钳电生理学方法研究了马软骨细胞K-ATP通道的生物物理特性。结果：针对K-ATP Kir6.1亚基的多克隆抗体在人和马软骨细胞中高水平表达，主要表达在正常软骨的浅表和中间区。在骨关节炎（OA）软骨的浅表软骨细胞中也检测到Kir6.1。在马软骨细胞的单通道电生理研究中，我们发现K-ATP通道的最大单一电导为47 +/- 9 pS (n = 5)，表达密度与可兴奋细胞相当。结论：我们首次在软骨细胞中发现功能性K-ATP通道。这表明K-ATP通道通过感知细胞外葡萄糖和细胞内三磷酸腺苷（ATP）水平参与软骨细胞代谢和电活动的偶联。OA软骨细胞中K-ATP通道表达的改变可能导致细胞内ATP感知和最佳代谢调节受损。(C) 2006国际骨关节炎学会。Elsevier Ltd.出版。版权所有。
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. (C) 2006 Ostecarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.