Abstract
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, Ca(2+) imaging, single molecule monitoring, immunocytochemical, and molecular methods to investigate regulation of the resting membrane potential (E(R)) and intracellular Ca(2+) 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 Ca(2+)-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 Ca(2+) influx through store-operated Ca(2+) channels. Some of the findings are illustrated in this review. Our summary diagram suggests that, in chondrocytes, the K(+) and Ca(2+) channels are linked in a positive feedback loop that can augment Ca(2+) influx and therefore regulate lubricant and cytokine secretion and gene transcription.