Activation of calcium entry in human carcinoma A431 cells by store depletion and phospholipase C-dependent mechanisms converge on ICRAC-like calcium channels

Elena Kaznacheyeva, Alexander Zubov, Konstantin Gusev, Ilya Bezprozvanny, Galina N. Mozhayeva

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Activation of phospholipase C in nonexcitable cells causes the release of calcium (Ca2+) from intracellular stores and activation of Ca2+ influx by means of Ca2+ release-activated channel (ICRAC) in the plasma membrane. The molecular identity and the mechanism of ICRAC channel activation are poorly understood. Using the patch-clamp technique, here we describe the plasma membrane Ca2+ channels in human carcinoma A431 cells, which can be activated by extracellular UTP, by depletion of intracellular Ca2+ stores after exposure to the Ca2+-pump inhibitor thapsigargin, or by loading the cells with Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate. The observed channels display the same conductance and gating properties as previously described Imin channels, but have significantly lower conductance for monovalent cations than the ICRAC channels. Thus, we concluded that the depletion-activated Ca2+ current in A431 cells is supported by ICRAC-like (ICRACL) channels, identical to Imin. We further demonstrated synergism in activation of ICRACL Ca2+ channels by extracellular UTP and intracellular inositol (1,4,5)-triphosphate (IP3), apparently because of reduction in phosphatidylinositol 4,5-bisphosphate (PIP2) levels in the patch. Prolonged exposure of patches to thapsigargin renders ICRACL Ca2+ channels unresponsive to IP3 but still available to activation by the combined action of IP3 and anti-PIP2 antibody. Based on these data, we concluded that phospholipase C-mediated and store-operated Ca2+ influx pathways in A431 cells converge on the same ICRACL Ca2+ channel, which can be modulated by PIP2.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number1
StatePublished - Jan 2 2001

ASJC Scopus subject areas

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