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Calcium phosphate complexation in ISOC channel inactivation
Author(s) -
Chen Hairu,
Wu Songwei,
Stevens Troy,
Cioffi Donna L.
Publication year - 2008
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.22.1_supplement.1178.17
Subject(s) - transient receptor potential channel , calcium , chemistry , biophysics , phosphorylation , trpc , trpc1 , voltage dependent calcium channel , biochemistry , calcium channel , microbiology and biotechnology , receptor , biology , organic chemistry
The endothelial ISOC channel is a calcium selective store‐operated calcium entry channel comprised of the transient receptor potential canonical (TRPC) proteins 1 and 4. Activation/inactivation properties are important determinants of channel function. ISOC inactivation is broadly described as fast or slow, and we have observed that the endothelial ISOC exhibits a slow inactivation. While it is known that ISOC inactivation is phosphorylation dependent and calcium dependent, it is not known whether the phosphorylation and calcium mediated pathways are part of a common mechanism. Indeed TRPC4 is phosphorylated upon thapsigargin‐induced activation of SOC entry. We hypothesized that free calcium permeating the ISOC channel pore complexes with the phosphate groups located in a proline rich region of TRPC4 to promote channel inactivation. As proof of concept, peptides corresponding to the proline rich region of TRPC4, with and without phosphorylated serine, were generated and isothermal calorimetry studies initiated to determine whether formation of a calcium‐phosphate complex is thermodynamically favorable. A rapid calorimetric transition was detected with phosphorylated peptide upon calcium addition. This observation is consistent with the idea that tight binding occurs between calcium and the phosphate group which is important in ISOC channel inactivation. Supported by HL60024 and 1F32HL086124.