Intracellular Ca2+ pools in PC12 cells. A unique, rapidly exchanging pool is sensitive to both inositol 1,4,5-trisphosphate and caffeine-ryanodine

J Biol Chem. 1991 Oct 25;266(30):20152-8.


Release of Ca2+ from intracellular stores was studied in the parent PC12 cell line and in recently isolated clones sensitive or insensitive to caffeine. In the caffeine-sensitive cells the cytosolic free Ca2+ concentration ([Ca2+]i) responses by the xanthine drug and by stimulants of receptors coupled to inositol 1,4,5-trisphosphate (Ins-P3) generation (bradykinin, ATP) depend on separate pathways because 1) caffeine does not stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate and 2) Ca(2+)-induced Ca2+ release, the process activated by caffeine, plays no major role in the Ins-P3-induced Ca2+ mobilization. Although distinct, these two mechanisms converge onto the same Ca2+ store. In fact 1) the [Ca2+]i responses by receptor agonists and caffeine were not additive; 2) either type of agent reduced (up to complete inhibition) the response to a subsequent administration of the same or the other agent; 3) all these responses were prevented by selective Ca2+ ATPase blockers; 4) ryanodine, which affects the intracellular Ca2+ channel sensitive to caffeine, also induced depletion of the receptor-sensitive Ca2+ pool; 5) in the 10 PC12 clones tested, sensitivity to caffeine paralleled ryanodine sensitivity. Therefore, PC12 cells, similar to some smooth muscle fibers but at variance with neurons and other secretory cells, express a single, rapidly exchanging Ca2+ store in which two distinct intracellular Ca2+ channels, i.e. the receptors for caffeine-ryanodine and Ins-P3, appear to be colocalized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines
  • Bradykinin / pharmacology
  • Caffeine / pharmacology*
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / antagonists & inhibitors
  • Cell Line
  • Cyclic AMP / metabolism
  • Diglycerides / metabolism
  • Fluorescent Dyes
  • Fura-2
  • Hydrolysis
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Ionomycin / pharmacology
  • Ryanodine / pharmacology*


  • Aminoquinolines
  • Diglycerides
  • Fluorescent Dyes
  • Ryanodine
  • Caffeine
  • Ionomycin
  • Inositol 1,4,5-Trisphosphate
  • Cyclic AMP
  • Calcium-Transporting ATPases
  • Quin2
  • Bradykinin
  • Calcium
  • Fura-2