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

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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ASJC Scopus subject areas

  • Biochemistry

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