Receptor-activated Ca2+ influx

Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells

Emilio Clementi, Heimo Scheer, Daniele Zacchetti, Cristina Fasolato, Tullio Pozzan, Jacopo Meldolesi

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Receptor-activated Ca2+ influx was investigated in PC12 cells clones loaded with fura-2. Cells were stimulated in a Ca2+-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 Ca2+-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.

Original languageEnglish
Pages (from-to)2164-2172
Number of pages9
JournalJournal of Biological Chemistry
Volume267
Issue number4
Publication statusPublished - Feb 5 1992

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PC12 Cells
Carbachol
Atropine
Clone cells
Chemical activation
Protective Devices
Safety devices
Phosphatidylinositol Phosphates
Ryanodine
Ryanodine Receptor Calcium Release Channel
Inositol 1,4,5-Trisphosphate
Thapsigargin
Calcium-Transporting ATPases
Fura-2
Type C Phospholipases
Phorbol Esters
Colforsin
Caffeine
GTP-Binding Proteins
Cations

ASJC Scopus subject areas

  • Biochemistry

Cite this

Receptor-activated Ca2+ influx : Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells. / Clementi, Emilio; Scheer, Heimo; Zacchetti, Daniele; Fasolato, Cristina; Pozzan, Tullio; Meldolesi, Jacopo.

In: Journal of Biological Chemistry, Vol. 267, No. 4, 05.02.1992, p. 2164-2172.

Research output: Contribution to journalArticle

Clementi, Emilio ; Scheer, Heimo ; Zacchetti, Daniele ; Fasolato, Cristina ; Pozzan, Tullio ; Meldolesi, Jacopo. / Receptor-activated Ca2+ influx : Two independently regulated mechanisms of influx stimulation coexist in neurosecretory PC12 cells. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 4. pp. 2164-2172.
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