Antagonists inactivate the inositol 1,4,5-trisphosphate (Ins-1,4,5-P3)- dependent Ca2+ channel independent of Ins-1,4,5-P3 metabolism

B. X. Zhang, G. Tortorici, X. Xu, S. Muallem

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Streptolysin O-permeable pancreatic acini, which retain intact signaling systems, were used to study the regulation of the inositol 1,4,5- trisphosphate (Ins-1,4,5-P3)-activated Ca2+ channel during agonist stimulation, and antagonist inhibition. Stimulation of permeable cells with carbachol induced rapid Ca2+ release from internal stores. Addition of heparin prior to or after agonist stimulation inhibited the release, indicating the activation of the Ins-1,4,5-P3-dependent Ca2+ channels by the agonist. Termination of cell stimulation with the specific antagonist atropine rapidly inactivated the release channels. Channel inactivation by the antagonist was independent of Ins-1,4,5-P3 levels since (a) addition of atropine to carbachol-stimulated cells resulted in a slow hydrolysis of Ins- 1,4,5-P3, (b) addition of 10-fold excess Ins-1,4,5-P3 together with the agonist did not prevent channel inactivation by the antagonist, and (c) the antagonist inactivated Ca2+ release in the presence of saturating concentration of the nonhydrolyzable Ins-1,4,5-P3. Hence, the antagonist appears to stabilize the Ins-1,4,5-P3-activated Ca2+ channel in a state refractory to Ins-1,4,5-P3. These findings are the first direct evidence that the channel can exist in such a refractory state.

Original languageEnglish (US)
Pages (from-to)17132-17135
Number of pages4
JournalJournal of Biological Chemistry
Issue number25
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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