Receptor-activated Ca2+ influx. Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells

J Biol Chem. 1992 Feb 5;267(4):2164-72.

Abstract

Receptor-activated Ca2+ influx was investigated in PC12 cells clones loaded with fura-2. Cells were stimulated in a Ca(2+)-free medium and studied after reintroduction of the cation or addition of Mn2+ into the medium. A first influx component, independent of receptor activation and sustained by depletion of the intracellular inositol 1,4,5-trisphosphate sensitive Ca2+ store (store-dependent Ca2+ influx, SDCI), was identified by experiments with carbachol followed by atropine and with agents that induce store discharge without polyphosphoinositide hydrolysis: thapsigargin, an inhibitor of Ca(2+)-ATPase activity; ryanodine and caffeine, activators of the ryanodine receptor. A second component of Ca2+ influx, induced by carbachol and rapidly blocked by atropine, relies on receptor-effector coupling via G protein(s) different from that (those) involved in phospholipase C activation. SDCI and receptor-coupled influx are similar in their voltage dependence and insensitivity to forskolin and phorbol esters but they differ with respect to their Mn2+ permeability and their sensitivity to the SC 38249 imidazole blocker. The two components might play different roles. SDCI might act as a safety device to prevent Ca2+ store depletion whereas receptor-dependent influx might control physiological functions such as secretion and growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Bradykinin / pharmacology
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism
  • Carbachol / pharmacology
  • Fura-2
  • Imidazoles / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Neurons / metabolism*
  • PC12 Cells
  • Receptors, Cell Surface / metabolism
  • Ryanodine / pharmacology
  • Signal Transduction*
  • Terpenes / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thapsigargin
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Imidazoles
  • Receptors, Cell Surface
  • Terpenes
  • Virulence Factors, Bordetella
  • Ryanodine
  • Caffeine
  • Thapsigargin
  • Atropine
  • 1-(2,3-bis((4-methoxyphenyl)methoxy)propyl)-1H-imidazole
  • Inositol 1,4,5-Trisphosphate
  • Carbachol
  • Calcium-Transporting ATPases
  • Tetradecanoylphorbol Acetate
  • Bradykinin
  • Calcium
  • Fura-2

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