RATIONALE Inositol 1,4,5-trisphosphate (IP(3))-induced vasoconstriction can occur independently of intracellular Ca(2+) release and via IP(3) receptor (IP(3)R) and canonical transient receptor potential (TRPC) channel activation, but functional signaling mechanisms mediating this effect are unclear. OBJECTIVES Study mechanisms by which IP(3)Rs stimulate TRPC channels in myocytes of resistance...

BACKGROUND Prolonged intracellular calcium elevation contributes to sensitization of nociceptors and chronic pain in inflammatory conditions. The underlying molecular mechanisms remain unknown but store-operated calcium entry (SOCE) components participate in calcium homeostasis, potentially playing a significant role in chronic pain pathologies. Most G protein-coupled receptors activated by inf...

BACKGROUND/AIMS Canonical transient receptor potential (TRPC) channels modulate membrane potential and intracellular Ca(2+). We examined the role of TRPC1 and TRPC3 channels in vasocontraction and relaxation in mouse aorta. METHODS Vasocontraction and relaxation of aorta from wild-type (WT), TRPC1 KO and TRPC3 knockout (KO) mice were measured for phenylephrine (Phe) and carbachol (CCh). Intra...

Members of the canonical transient receptor potential (TRPC) subfamily of cation channels are candidates for capacitative and non-capacitative Ca2+ entry channels. When ectopically expressed in cell lines, TRPC3 can be activated by phospholipase C-mediated generation of diacylglycerol or by addition of synthetic diacylglycerols, independently of Ca2+ store depletion. Apart from this mode of reg...

In previous studies using mice with macrophage-specific loss of TRPC3 we found a significant, selective effect of TRPC3 on the biology of M1, or inflammatory macrophages. Whereas activation of some components of the unfolded protein response and the pro-apoptotic mediators CamkII and Stat1 was impaired in Trpc3-deficient M1 cells, gathering insight about other molecular signatures within macrop...

Store-operated Ca(2+) channels (SOCs) mediate receptor-stimulated Ca(2+) influx. Accumulating evidence indicates that members of the transient receptor potential (TRP) channel family are components of SOCs in mammalian cells. Agonist stimulation activates SOCs and TRP channels directly and by inducing translocation of channels in intracellular vesicles to the plasma membrane (PM). The mechanism...

In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages,...

Results Elimination of Ca permeation through TRPC3 abrogated its ability to trigger NFAT translocation in both HEK293 cells and in HL-1 atrial myocytes. Wild-type TRPC3 was found capable of initiating NFAT translocation in atrial myocytes by a small, homogenous elevation of cytoplasmic Ca that was independent of voltagegated CaV1.2 channels. By contrast, a Ca 2+ impermeant TRPC3 mutant strongly...

TRPC3 has been suggested as a key component of phospholipase C-dependent Ca signaling. Here we investigated the role of TRPC3-mediated Na entry as a determinant of plasmalemmal Na /Ca exchange. Ca signals generated by TRPC3 overexpression in HEK293 cells were found to be dependent on extracellular Na , in that carbachol-stimulated Ca entry into TRPC3 expressing cells was significantly suppresse...

Canonical transient receptor potential (TRPC) channels are Ca2+-permeable nonselective cation channels that are widely expressed in numerous cell types. Seven different members of TRPC channels have been isolated. The activity of these channels is regulated by the filling state of intracellular Ca2+ stores and/or diacylglycerol and/or Ca2+/calmodulin. However, no evidence is available as to whe...