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Wakabayashi, I; Marumo, M; Graziani, A; Poteser, M; Groschner, K.
TRPC4 expression determines sensitivity of the platelet-type capacitative Ca2+ entry channel to intracellular alkalosis.
Platelets. 2006; 17(7):454-461 Doi: 10.1080/09537100600757489
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Co-Autor*innen der Med Uni Graz
Groschner Klaus
Poteser Michael
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Abstract:
The present study was designed to analyze the molecular basis of the intracellular pH-dependent capacitative Ca2+ entry (CCE) of human platelets and megakaryocytic cells, specifically to test the hypothesis that members of the classical transient receptor potential (TRPC) protein family are involved in the CCE pathway that is promoted by intracellular alkalosis. Human platelets as well as the tested megakaryocytic cell lines (CMK cells, MEG-01 cells) and HEK293 cells displayed thapsigargin-induced CCE and responded to monensin with comparable elevation in intracellular pH. Promotion of CCE by monensin-induced intracellular alkalosis, however, was profound in mature platelets, moderate in CMK cells and lacking in MEG-01 cells as well as in HEK293 cells. Analysis of the TRPC expression pattern by immunoblotting revealed that mature platelets and CMK cells express TRPC4 along with TRPC1 and TRPC3, while TRPC4 is lacking in MEG-01 cells. HEK293 cells displayed CCE characteristics as well as lack of TRPC4 expression similar to MEG-01 cells. Over-expression of TRPC4 in HEK293 cells was found to result in a gain of pH-sensitivity of CCE with clearly detectable promotion of CCE in response to monensin. These results suggest that platelet CCE channel complexes contain TRPC4 as a molecular component that determines sensitivity of CCE to intracellular alkalosis.
Find related publications in this database (using NLM MeSH Indexing)
Alkalosis -
Blood Cells -
Blood Platelets - chemistry
Calcium - metabolism
Calcium Channels - analysis
Cell Line -
Humans -
Hydrogen-Ion Concentration -
Megakaryocytes - chemistry
Monensin - pharmacology
TRPC Cation Channels - analysis
Thapsigargin - pharmacology

Find related publications in this database (Keywords)
platelets
megakaryocytes
intracellular alkalosis
transient receptor potential channels
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