Functional coupling of secretion and capacitative calcium entry in PC12 cells

The caffeine evoked effects on the intracellular Ca²⁺ concentration ([Ca²⁺]i) and on the release of dopamine by PC12 cells were investigated. Stimulation by caffeine resulted in a transient Ca²⁺ release which was followed by a sustained phase of Ca²⁺ entry through a non-voltage dependent pathway. Treatment with cyclopiazonic acid (CPA) or thapsigargin, inhibitors of the Ca²⁺ ATPase pump of the endoplasmic reticulum, resulted in only a sustained rise in [Ca²⁺]i in the presence of extracellular Ca²⁺. Pretreatment of cells with CPA or thapsigargin abolished the subsequent Ca²⁺ responses to caffeine. Caffeine also evoked the release of dopamine from the cells only in the presence of extracellular Ca²⁺, which was mimicked by CPA. These results suggest that store-dependent Ca²⁺ entry evoked by caffeine has an indispensable role in the secretory response in an excitable cell line, PC12 cells.