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K+ and Ca2+ Channels Regulate Ca2+ Signaling in Chondrocytes: An Illustrated Review

1
Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan
2
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada
*
Author to whom correspondence should be addressed.
Cells 2020, 9(7), 1577; https://doi.org/10.3390/cells9071577 (registering DOI)
Received: 13 May 2020 / Revised: 23 June 2020 / Accepted: 25 June 2020 / Published: 29 June 2020
(This article belongs to the Special Issue Ion Channels in Non-excitable Cells of the Musculoskeletal System)
An improved understanding of fundamental physiological principles and progressive pathophysiological processes in human articular joints (e.g., shoulders, knees, elbows) requires detailed investigations of two principal cell types: synovial fibroblasts and chondrocytes. Our studies, done in the past 8–10 years, have used electrophysiological, Ca2+ imaging, single molecule monitoring, immunocytochemical, and molecular methods to investigate regulation of the resting membrane potential (ER) and intracellular Ca2+ levels in human chondrocytes maintained in 2-D culture. Insights from these published papers are as follows: (1) Chondrocyte preparations express a number of different ion channels that can regulate their ER. (2) Understanding the basis for ER requires knowledge of (a) the presence or absence of ligand (ATP/histamine) stimulation and (b) the extraordinary ionic composition and ionic strength of synovial fluid. (3) In our chondrocyte preparations, at least two types of Ca2+-activated K+ channels are expressed and can significantly hyperpolarize ER. (4) Accounting for changes in ER can provide insights into the functional roles of the ligand-dependent Ca2+ influx through store-operated Ca2+ channels. Some of the findings are illustrated in this review. Our summary diagram suggests that, in chondrocytes, the K+ and Ca2+ channels are linked in a positive feedback loop that can augment Ca2+ influx and therefore regulate lubricant and cytokine secretion and gene transcription. View Full-Text
Keywords: chondrocyte; OUMS-27; resting membrane potential; Ca2+ signaling; Ca2+ release-activated Ca2+ channel; Ca2+-activated K+ channel; total internal reflection fluorescence microscopy chondrocyte; OUMS-27; resting membrane potential; Ca2+ signaling; Ca2+ release-activated Ca2+ channel; Ca2+-activated K+ channel; total internal reflection fluorescence microscopy
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MDPI and ACS Style

Suzuki, Y.; Yamamura, H.; Imaizumi, Y.; Clark, R.B.; Giles, W.R. K+ and Ca2+ Channels Regulate Ca2+ Signaling in Chondrocytes: An Illustrated Review. Cells 2020, 9, 1577.

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