Ca2+ oscillations and intercellular Ca2+ waves in ATP-stimulated articular chondrocytes

Abstract

Cytosolic Ca2+ oscillations are known to occur in many cell types stimulated with agonists linked to the phosphoinositide signaling pathway. Trains of repetitive short-lasting Ca2+ spikes could be induced in articular chondrocytes by extracellular ATP, an agonist potently effective in stimulating cartilage resorption. The mechanism of these Ca2+ oscillations was studied by computerized video imaging on primary cultures of articular chondrocytes. Few cycles of oscillatory activity could be evoked in the absence of extracellular Ca2+, while, for oscillations to be sustained, Ca2+ influx was required. Thapsigargin irreversibly blocked Ca2+ oscillations, thus demonstrating the crucial involvement of intracellular stores in triggering the rhythmic activity. Apart from activating intracellular Ca2+ release, extracellular ATP also induced a noncapacitive Ca2+ influx in these cells. This ATP-mediated influx modulates both the oscillation frequency and intracellular stores refilling. In monolayers of confluent cells, Ca2+ oscillations spread from cell to cell in the form of intercellular waves. Propagating waves could also be observed in the absence of extracellular Ca2+, demonstrating that Ca2+ itself is not required for signal coordination. These results demonstrate that complex spatiotemporal pathways of Ca2+ oscillations and intercellular Ca2+ waves could be activated in articular chondrocytes during degenerative diseases.