The store-operated calcium entry pathways in human carcinoma A431 cells: Functional properties and activation mechanisms

Konstantin Gusev, Lyuba Glouchankova, Alexander Zubov, Elena Kaznacheyeva, Zhengnan Wang, Ilya Bezprozvanny, Galina N. Mozhayeva

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Activation of phospholipase C (PLC)-mediated signaling pathways in nonexcitable cells causes the release of Ca2+ from intracellular Ca2+ stores and activation of Ca2+ influx across the plasma membrane. Two types of Ca2+ channels, highly Ca2+-selective ICRAC and moderately Ca2+-selective ISOC, support store-operated Ca2+ entry process. In previous patch-clamp experiments with a human carcinoma A431 cell line we described store-operated Imin/ICRACL plasma membrane Ca2+ influx channels. In the present paper we use whole-cell and single-channel recordings to further characterize store-operated Ca2+ influx pathways in A431 cells. We discovered that (a) ICRAC and ISOC are present in A431 cells; (b) ICRAC currents are highly selective for divalent cations and fully activate within 150 s after initiation of Ca2+ store depletion; (c) ISOC currents are moderately selective for divalent cations (PBa/PCs 14.5) and require at least 300 s for full activation; (d) ICRAC and ISOC currents are activated by PLC-coupled receptor agonists; (e) ISOC currents are supported by Imin/ICRACL channels that display 8.5-10 pS conductance for sodium; (f) ICRAC single channel conductance for sodium is estimated at 0.9 pS by the noise analysis; (g) Imin/ICRACL channels are activated in excised patches by an amino-terminal fragment of InsP3R1 (InsP3R1N); and (h) InsP3 binding to InsP3R1N is necessary for activation of Imin/ICRACL channels. Our findings provide novel information about store-operated Ca2+ influx pathways in A431 cells.

Original languageEnglish (US)
Pages (from-to)81-94
Number of pages14
JournalJournal of General Physiology
Volume122
Issue number1
DOIs
StatePublished - Jul 1 2003

Keywords

  • Calcium channels
  • Calcium signaling
  • Inositol 1,4,5-trisphosphate
  • Patch-clamp
  • Whole-cell

ASJC Scopus subject areas

  • Physiology

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