Store depletion‐induced calcium influx in rat cerebellar astrocytes

In rat cerebellar astrocytes, intracellular Ca 2+ store depletion by receptor agonists or sarco(endo)plasmic reticulum Ca 2+ ATPase inhibitors induced a transient increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the absence of extracellular Ca 2+ and a sustained increase in its presence. After 10 min treatment with thapsigargin, the [Ca 2+ ] i was unaffected by removal of thapsigargin, but fell rapidly to the basal level when extracellular Ca 2+ was removed, suggesting the involvement of capacitative Ca 2+ entry (CCE); this effect was not seen until cells had been exposed to thapsigargin for at least 2 min. Using the whole cell voltage clamp technique, a 60 – 100 pA inward current was activated by store depletion, the reversal potential ranging from −5 to 0 mV. When extracellular Na + was isotonically replaced by Tris, the thapsigargin‐induced [Ca 2+ ] i increase was enhanced, while the inward current was reduced, indicating that store‐operated Ca 2+ channels were permeable to Na + ; however, they were not permeable to Sr 2+ or Ba 2+ . Thapsigargin‐induced CCE remained the same in the presence of nifedipine, La 3+ or Cd 2+ , while it was inhibited in the presence of SK&F96365. In cerebellar astrocytes, inhibition of protein serine/threonine phosphorylation promoted CCE. In conclusion, in rat cerebellar astrocytes, store depletion activated a CCE via channels which were permeable to Ca 2+ and Na + and regulated by phosphorylation.British Journal of Pharmacology (2002) 135 , 1383–1392; doi: 10.1038/sj.bjp.0704594