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Arachidonic acid induced calcium signaling at acidic pH (1057.2)
Author(s) -
Moss Nicholas,
Hou Bing,
Young Richard,
Bruns Alexander,
Wilson Lesley,
Beech David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1057.2
Subject(s) - trpc5 , trpc , arachidonic acid , chemistry , calcium in biology , calcium , umbilical vein , transient receptor potential channel , biochemistry , intracellular , microbiology and biotechnology , biology , receptor , in vitro , enzyme , organic chemistry
Arachidonic acid (AA) induces calcium signalling and downstream functional responses. It is often present in pathophysiological environments where there is also acidity, as in ischaemic tissues and tumours. The aim of our study was to investigate the relevance of the acidic environment to AA‐evoked responses. In intracellular Ca2+ measurement experiments, AA induced a small Ca2+ influx at pH 7.4 in human umbilical vein endothelial cells which was potentiated by almost an order of magnitude at pH 6.8. The response at pH 6.8 was not dependent on the AA‐activated channels TRPV4 or Orai3. Unexpectedly, inhibitor antibodies targeted to TRPC4 or TRPC5 suppressed the response. Furthermore, TRPC5 channels stably expressed in HEK293 cells were activated by AA at pH 6.8 but not 7.4. The data suggest that mild acidosis strongly potentiates the contribution of TRPC channels to AA responses. Grant Funding Source : Supported by the British Heart Foundation