Functional overlap of IP3- and cADP-ribose-sensitive calcium stores in guinea pig myenteric neurons

D. J. Turner, B. J. Segura, R. A. Cowles, W. Zhang, M. W. Mulholland

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

In myenteric neurons two different receptor subtypes govern the intracellular Ca2+ stores: the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and the ryanodine receptor (RyR). Their degree of functional overlap was determined by examining Ca2+ release in these cells through both superfusion techniques and intracellular microinjection. Microinjection of IP3 (50 μM) and cADP-ribose (cADPr, 50 μM), specific ligands for the IP3R and RyR, respectively, demonstrated mobilization of intracellular Ca2+ stores. Perfusion with cinnarizine (50 μM) or dantrolene (10 μM), antagonists of the IP3R and RyR, respectively, eliminated the Ca2+ response to microinjected IP3 and cADPr. Superfusion of the neurons with 100 μM ATP, an IP3-mediated Ca2+-mobilizing agonist, caused intracellular Ca2+ increments, which were antagonized by cinnarizine, and the RyR antagonists dantrolene, procaine (5 mM), and ryanodine (1 μM). Caffeine (10 mM) was applied repetitively in Ca2+-free conditions to deplete RyR-sensitive stores; subsequent perfusion with ATP demonstrated a Ca2+ response. Conversely, caffeine caused a Ca2+ response after repetitive ATP exposures. The internal Ca2+ stores of myenteric neurons are governed by two receptor subtypes, IP3R and RyR, which share partial functional overlap.

Original languageEnglish (US)
Pages (from-to)G208-G215
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number1 44-1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Adenosine 3′,5′-cyclic diphosphate-ribose
  • Calcium
  • Inositol 1,4,5-trisphosphate
  • Myenteric plexus
  • Ryanodine

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