Selective activation of Ca2+ influx by extracellular ATP in a pancreatic β-cell line (HIT)

Jean François Geschwind, Marcia Hiriart, Major C. Glennon, Habiba Najafi, Barbara E. Corkey, Franz M. Matschinsky, Marc Prentki

Research output: Contribution to journalArticle

Abstract

The action of exogenous ATP on cytoplasmic free Ca2+ ([Ca2+]i) was studied in insulin secreting cells using fura-2. Stimulation of clonal pancreatic β-cells (HIT) with ATP (range 2-20 μM) evoked a sustained elevation in [Ca2+]i. ATP selectively promoted Ca2+ influx and not Ca2+ mobilization since (1) the effect required external Ca2+ and (2) was observed in cells in which internal stores were depleted with ionomycin (3) the rate of Mn2+ influx, measured as the quenching of the fura-2 signal, was accelerated by ATP. The action of ATP was unaffected by the voltage-sensitive Ca2+ channel blockers nifedipine and verapamil as well as by a depolarizing concentration of K+. The effect on [Ca2+]i was highly specific for ATP since AMP, ADP, adenosine 5′-[γ-thio]triphosphate, adenosine 5′-[β-γ-methylene]triphosphate, GTP and adenosine were ineffective. In normal pancreatic islet cells, both exogenous ATP (range 0.2-2 μM) and ADP induced a transient Ca2+ elevation that did not require external Ca2+. The nucleotide specificity of the effect on [Ca2+]i suggests that ATP activates P2y purinergic receptors in normal β-cells. Thus, ATP evokes a Ca2+ signal in clonal HIT cells and normal islet cells by different transducing systems involving distinct purinoreceptors. A novel mechanism for increasing [Ca2+]i by extracellular ATP is reported in HIT cells, since the nucleotide specificity and the selective activation of Ca2+ influx without mobilization of internal Ca2+ stores cannot be explained by mechanism already described in other cell systems.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalBBA - Molecular Cell Research
Volume1012
Issue number1
DOIs
StatePublished - Jun 15 1989

Keywords

  • (Rat pancreatic β-cell line (HIT))
  • ATP, extracellular
  • Calcium ion
  • Receptor operated channels
  • cytoplasmic

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Geschwind, J. F., Hiriart, M., Glennon, M. C., Najafi, H., Corkey, B. E., Matschinsky, F. M., & Prentki, M. (1989). Selective activation of Ca2+ influx by extracellular ATP in a pancreatic β-cell line (HIT). BBA - Molecular Cell Research, 1012(1), 107-115. https://doi.org/10.1016/0167-4889(89)90018-9