Abstract
Chondrocytes in articular cartilage utilize mechanical signals from their environment to regulate their metabolic activity. However, the sequence of events involved in the transduction of mechanical signals to a biochemical signal is not fully understood. It has been proposed that an increase in the concentration of intracellular calcium ion ([Ca^2+^]~i~) is one of the earliest events in the process of cellular mechanical signal transduction. With use of fluorescent confocal microscopy, [Ca^2+^]~i~ was monitored in isolated articular chondrocytes subjected to controlled deformation with the edge of a glass micropipette. Mechanical stimulation resulted in an immediate and transient increase in [Ca^2+^]~i~. The initiation of Ca^2+^ waves was abolished by removing Ca^2+^ from the extracellular media and was significantly inhibited by the presence of gadolinium ion (10 μ__M__) or amiloride (1 m__M__), which have previously been reported to block mechanosensitive ion channels. Inhibitors of intracellular Ca^2+^ release (dantrolene and 8‐diethylaminooctyl 3,4,5‐trimethoxybenzoate hydrochloride) or cytoskeletal disrupting agents (cytochalasin D and colchicine) had no significant effect on the characteristics of the Ca^2+^ waves. These findings suggest that a possible mechanism of Ca^2+^ mobilization in this case is a self‐reinforcing influx of Ca^2+^ from the extracellular media, initiated by a Ca^2+^‐permeable mechanosensitive ion channel. Our results indicate that a transient increase in intracellular Ca^2+^ concentration may be one of the earliest events involved in the response of chondrocytes to mechanical stress and support the hypothesis that deformation‐induced Ca^2+^ waves are initiated through mechanosensitive ion channels.