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Permeable Cation Channel (permeable + cation_channel)
Selected AbstractsEndothelin-1 activates a Ca2+ -permeable cation channel with TRPC3 and TRPC7 properties in rabbit coronary artery myocytesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2007C. M. Peppiatt-Wildman In the present work we used patch pipette techniques to study the properties of a novel Ca2+ -permeable cation channel activated by the potent coronary vasoconstrictor endothelin-1 (ET-1) in freshly dispersed rabbit coronary artery myocytes. With cell-attached recording bath application of 10 nm ET-1 evoked cation channel currents (Icat) with subconductance states of about 18, 34 and 51 and 68 pS, and a reversal potential of 0 mV. ET-1 evoked channel activity when extracellular Ca2+ was the charge carrier, illustrating significant Ca2+ permeability. ET-1-induced responses were inhibited by the ETA receptor antagonist BQ123 and the phospholipase C (PLC) inhibitor U73122. The diacylglycerol analogue 1-oleoyl-2-acetyl- sn -glycerol (OAG) also stimulated Icat, but the protein kinase C (PKC) inhibitor chelerythrine did not inhibit either the OAG- or ET-1-induced Icat. Inositol 1,4,5-trisphosphate (IP3) did not activate Icat, but greatly potentiated the response to OAG and this effect was blocked by heparin. Bath application of anti-TRPC3 and anti-TRPC7 antibodies to inside-out patches markedly inhibited ET-1-evoked Icat, but antibodies to TRPC1, C4, C5 and C6 had no effect. Immunocytochemical studies demonstrated preferential TRPC7 expression in the plasmalemma, whereas TRPC3 was distributed throughout the myocyte, and moreover co-localization of TRPC3 and TRPC7 signals was observed at, or close to, the plasma membrane. Flufenamic acid, Gd3+, La3+ and extracellular Ca2+ inhibited Icat with IC50 values of 2.45 ,m, 3.8 ,m, 7.36 ,m and 22 ,m, respectively. These results suggest that in rabbit coronary artery myocytes ET-1 evokes a Ca2+ -permeable non-selective cation channel with properties similar to TRPC3 and TRPC7, and indicates that these proteins may be important components of this conductance. [source] Antagonist effect of flufenamic acid on TRPM2 cation channels activated by hydrogen peroxideCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2007Mustafa Naz Abstract The melastatin-related transient receptor potential channel TRPM2 is a plasma membrane Ca2+ -permeable cation channel that is activated by hydrogen peroxide (H2O2) as a consequence of oxidative stress although the channel activation by H2O2 appears to represent a cell-specific process in cells with endogenous expression of TRPM2. Flufenamic acid (FA) is a non-steroidal anti-inflammatory compound. Whether H2O2 activates or FA inhibits TRPM2 channels in Chinese hamster ovary (CHO) cell is currently unknown. Due to lack of known antogonists of this channel, we demonstrate in CHO cells that FA inhibits TRPM2 activated by extracellular H2O2. CHO cells were transfected with cDNA coding for TRPM2. Cells were studied with the conventional whole-cell patch clamp technique. The intracellular solution used EDTA (10,mM) as chelator for Ca2+ and heavy metal ions. H2O2 (10,mM) and FA (0.1,mM) were applied extracellularly. Non-selective cation currents were consistently induced by H2O2. The time cause of H2O2 effects was characterized by a delay of 2,5,min and a slow current induction to reach a plateau. The H2O2 - induced inward current was effectively inhibited by 0.1,mM FA applied extracellularly. In conclusion, we have demonstrated that FA is an effective antogonist of TRPM2 channels and H2O2activated currents in CHO cells. FA in CHO cells may be considered, at best, a starting point for the development of TRPM2 channel blockers. Copyright © 2006 John Wiley & Sons, Ltd. [source] Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cellsCELL PROLIFERATION, Issue 3 2008G. Aguiari Objectives: Polycystin-1 (PC1), a signalling receptor regulating Ca2+ -permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca2+ entry (NCCE) and Ca2+ oscillations, with downstream effects on cell proliferation. Results and discussion: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum-induced Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ oscillations and cell proliferation are increased in PC1-mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease. [source] | ||||||||||