Asymmetrical, agonist-induced fluctuations in local extracellular [Ca2+] in intact polarized epithelia

Rosa Caroppo, Andrea Gerbino, Lucantonio Debellis, Olga Kifor, David I. Soybel, Edward M. Brown, Aldebaran M. Hofer, Silvana Curci

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Abstract

We recently proposed that extracellular Ca2+ ions participate in a novel form of intercellular communication involving the extracellular Ca2+ sensing receptor (CaR). Here, using Ca2+ selective microelectrodes, we directly measured the profile of agonist-induced [Ca2+]ext changes in restricted domains near the basolateral or luminal membranes of polarized gastric acid-secreting cells. The Ca2+-mobilizing agonist carbachol elicited a transient, La3+-sensitive decrease in basolateral [Ca2+] (average ≈250 μM, but as large as 530 μM). Conversely, carbachol evoked an HgCl2-sensitive increase in [Ca2+] (average ≈400 μM, but as large as 520 μM) in the lumen of single gastric glands. Both responses were significantly reduced by pretreatment with sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pump inhibitors or with the intracellular Ca2+ chelator BAPTA-AM. Immunofluorescence experiments demonstrated an asymmetric localization of plasma membrane Ca2+ ATPase (PMCA), which appeared to be partially co-localized with CaR and the gastric H+/K+-ATPase in the apical membrane of the acid-secreting cells. Our data indicate that agonist stimulation results in local fluctuations in [Ca2+]ext that would be sufficient to modulate the activity of the CaR on neighboring cells.

Original languageEnglish (US)
Pages (from-to)6316-6326
Number of pages11
JournalEMBO Journal
Volume20
Issue number22
DOIs
StatePublished - Nov 15 2001

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Caroppo, R., Gerbino, A., Debellis, L., Kifor, O., Soybel, D. I., Brown, E. M., Hofer, A. M., & Curci, S. (2001). Asymmetrical, agonist-induced fluctuations in local extracellular [Ca2+] in intact polarized epithelia. EMBO Journal, 20(22), 6316-6326. https://doi.org/10.1093/emboj/20.22.6316