Amplitude modulation of Ca2+ signals induced by histamine in human endothelial cells

Masahiro Oike, Guy Droogmans, Bernd Nilius

Research output: Contribution to journalArticle

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Abstract

We have addressed the problem of whether the agonist concentration sensed by endothelial cells is encoded by the sustained rise of the intracellular Ca2+ concentration ([Ca2+]i) or by the frequency of intracellular Ca2+ oscillations. Single or confluent endothelial cells from umbilical veins were stimulated for 15 min with histamine (0.03 to 100 μmol/l), and the concomitant changes in [Ca2+]i were measured with fura-2/AM. Application of histamine at concentrations above 0.1 μmol/l resulted always in a fast spike of [Ca2+]i, followed by a slow decline to a sustained plateau level, which depends on the presence of extracellular Ca2+. At the same time of the development of this plateau phase, quenching of the fura-2/AM signal occurred during agonist stimulation in a Ca2+-free, 1.5 mmol/l Mn2+ containing solution, indicating influx of divalent cations during this time. From 48 cells in 1.5 mmol/l [Ca2+]e we obtained a close relation between histamine concentration and time integral of [Ca2+]i taken over the 15 min recording of the plateau [Ca2+]i. The half-maximal increase in the integral of [Ca2+]i was at 0.7 μmol/l for solitary cells, 1.2 μmol/l for clustered cells and 1.2 μmol/l for the plateau Ca2+ level. Repetitive Ca2+ spikes or Ca2+ oscillations appeared only in 16 out of 48 cells, but their frequency was not correlated to the agonist concentration. Ca2+ oscillations were only observed in a concentration window between 0.1 and 1 μmol/l histamine, both in single and in clustered endothelial cells. Our results indicate that coding of the agonist concentration in endothelial cells is not related to the frequency of Ca2+ oscillations, but is closely correlated with the plateau level of intracellular Ca2+.

Original languageEnglish
Pages (from-to)287-291
Number of pages5
JournalBBA - Molecular Cell Research
Volume1222
Issue number2
DOIs
Publication statusPublished - Jun 30 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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