Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.
Abstract: 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.
Publication Date: 2006-08-07 PubMed ID: 16891130DOI: 10.1016/j.joca.2006.06.017Google Scholar: Lookup
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- Journal Article
Summary
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This study reveals the presence of functional ATP-sensitive potassium channels known as K(ATP) channels in human and horse cartilage cells, which may serve a role in linking metabolism and cell activity by sensing levels of extracellular glucose and intracellular ATP. An altered expression of these channels in osteoarthritis cartilage could potentially affect internal ATP detection and optimal metabolic regulation.
Study Objective and Method:
- The research aimed to explore the existence of K(ATP) channels in chondrocytes, the cells found in healthy cartilage, and investigate their functionality. These channels are known to be present in some organs such as pancreas, heart, and brain and are thought to contribute to the detection of variations in the metabolic state of those organs.
- The study utilized Immunohistochemistry, a technique that uses antibodies to detect the presence of specific proteins in cells of a tissue section, to investigate the expression of K(ATP) channels in chondrocytes of humans and horses.
- The biophysical properties of these channels in horse chondrocytes were further examined using patch-clamp electrophysiology, a method that allows the study of individual or multiple ion channels in cells.
Results and Findings:
- The study demonstrated the presence of K(ATP) channels in both human and horse chondrocytes, largely in the superficial and middle zones of normal cartilage.
- These channels were also found in osteoarthritic (OA) cartilage, indicating their potential involvement in arthritis development or progression.
- Electrophysiological investigations revealed the properties of these channels, with a maximum unitary conductance of 47 +/- 9 pS. The density of channel expression was analogous to that seen in excitable cells, which are cells capable of generating and conducting electrical signals.
Conclusion and Implication:
- This is the first ever study to demonstrate functional K(ATP) channels in chondrocytes, suggesting their crucial role in connecting metabolic and electrical activities in these cells.
- These channels appear to sense extracellular glucose and intracellular ATP levels, indicating their potential significance in metabolic regulation.
- Any alteration in the expression of these channels in chondrocytes of OA cartilage may result in impaired sensing of internal ATP and subsequent optimum metabolic regulation. This can have implications in understanding and possibly treating disorders like osteoarthritis.
Cite This Article
APA
Mobasheri A, Gent TC, Nash AI, Womack MD, Moskaluk CA, Barrett-Jolley R.
(2006).
Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.
Osteoarthritis Cartilage, 15(1), 1-8.
https://doi.org/10.1016/j.joca.2006.06.017 Publication
Researcher Affiliations
- Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, UK.
MeSH Terms
- Adenosine Triphosphate / metabolism
- Animals
- Cartilage, Articular / metabolism
- Chondrocytes / metabolism
- Horses
- Humans
- Immunohistochemistry
- Membrane Potentials / physiology
- Osteoarthritis / physiopathology
- Patch-Clamp Techniques
- Potassium Channels, Inwardly Rectifying / metabolism
- Potassium Channels, Inwardly Rectifying / physiology
Citations
This article has been cited 13 times.- Takács R, Kovács P, Ebeid RA, Almássy J, Fodor J, Ducza L, Barrett-Jolley R, Lewis R, Matta C. Ca(2+)-Activated K(+) Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review. Int J Mol Sci 2023 Apr 5;24(7).
- Seda M, Geerlings M, Lim P, Jeyabalan-Srikaran J, Cichon AC, Scambler PJ, Beales PL, Hernandez-Hernandez V, Stoker AW, Jenkins D. An FDA-Approved Drug Screen for Compounds Influencing Craniofacial Skeletal Development and Craniosynostosis. Mol Syndromol 2019 Feb;10(1-2):98-114.
- Maleckar MM, Clark RB, Votta B, Giles WR. The Resting Potential and K(+) Currents in Primary Human Articular Chondrocytes. Front Physiol 2018;9:974.
- Lewis R, Barrett-Jolley R. Changes in Membrane Receptors and Ion Channels as Potential Biomarkers for Osteoarthritis. Front Physiol 2015;6:357.
- Li X, Liu C, Liang W, Ye H, Chen W, Lin R, Li Z, Liu X, Wu M. Millimeter wave promotes the synthesis of extracellular matrix and the proliferation of chondrocyte by regulating the voltage-gated K+ channel. J Bone Miner Metab 2014 Jul;32(4):367-77.
- Staunton CA, Lewis R, Barrett-Jolley R. Ion channels and osteoarthritic pain: potential for novel analgesics. Curr Pain Headache Rep 2013 Dec;17(12):378.
- Rufino AT, Rosa SC, Judas F, Mobasheri A, Lopes MC, Mendes AF. Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing. J Cell Biochem 2013 Aug;114(8):1879-89.
- Mobasheri A, Lewis R, Ferreira-Mendes A, Rufino A, Dart C, Barrett-Jolley R. Potassium channels in articular chondrocytes. Channels (Austin) 2012 Nov-Dec;6(6):416-25.
- Lewis R, Feetham CH, Gentles L, Penny J, Tregilgas L, Tohami W, Mobasheri A, Barrett-Jolley R. Benzamil sensitive ion channels contribute to volume regulation in canine chondrocytes. Br J Pharmacol 2013 Apr;168(7):1584-96.
- Hdud IM, El-Shafei AA, Loughna P, Barrett-Jolley R, Mobasheri A. Expression of Transient Receptor Potential Vanilloid (TRPV) channels in different passages of articular chondrocytes. Int J Mol Sci 2012;13(4):4433-4445.
- Barrett-Jolley R, Lewis R, Fallman R, Mobasheri A. The emerging chondrocyte channelome. Front Physiol 2010;1:135.
- Lewis R, Asplin KE, Bruce G, Dart C, Mobasheri A, Barrett-Jolley R. The role of the membrane potential in chondrocyte volume regulation. J Cell Physiol 2011 Nov;226(11):2979-86.
- Mobasheri A, Lewis R, Maxwell JE, Hill C, Womack M, Barrett-Jolley R. Characterization of a stretch-activated potassium channel in chondrocytes. J Cell Physiol 2010 May;223(2):511-8.
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