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

• Main Authors: Yoshiaki Suzuki, Hisao Yamamura, Yuji Imaizumi, Robert B. Clark, Wayne R. Giles
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Cells
• Subjects: chondrocyte; OUMS-27; resting membrane potential; Ca2+ signaling; Ca2+ release-activated Ca2+ channel; Ca2+-activated K+ channel
• Online Access: https://www.mdpi.com/2073-4409/9/7/1577
• ISSN: 2073-4409

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 (E_R) 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 E_R. (2) Understanding the basis for E_R 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 E_R. (4) Accounting for changes in E_R 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.