50 results match your criteria permeability trpc4

Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.

Arch Pharm Res 2021 Mar 24. Epub 2021 Mar 24.

Department of Pharmacology and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

Canonical transient receptor potential channels (TRPCs) are nonselective, high calcium permeability cationic channels. The TRPCs family includes TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7. These channels are widely expressed in the cardiovascular and nervous systems and exist in many other human tissues and cell types, playing several crucial roles in the human physiological and pathological processes. Read More

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Chromogranin A (CGA)-derived polypeptide (CGA) inhibits TNF-α-induced vascular endothelial hyper-permeability through SOC-related Ca signaling.

Peptides 2020 09 5;131:170297. Epub 2020 May 5.

Department of Emergency, The Third People's Hospital of Chengdu, The Second Affiliated Chengdu Clinical College of Chongqing Medical University, Chengdu, Sichuan 610031, PR China.

CGA (Vasostatin-1, VS-1) a N-terminal Chromogranin A (CGA)-derived peptide, has been shown to have a protective effect against TNF-α-induced impairment of endothelial cell integrity. However, the mechanisms of this effect have not yet been clarified. CGA (Chromofungin, CHR) is an important bioactive fragment of CGA. Read More

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September 2020

Analysis of interaction between intracellular spermine and transient receptor potential canonical 4 channel: multiple candidate sites of negatively charged amino acids for the inward rectification of transient receptor potential canonical 4.

Korean J Physiol Pharmacol 2020 Jan 20;24(1):101-110. Epub 2020 Dec 20.

Department of Physiology, College of Medicine, Seoul National University, Seoul 03080, Korea.

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Read More

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January 2020

Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels.

Hussein N Rubaiy

Br J Pharmacol 2019 04 6;176(7):832-846. Epub 2019 Mar 6.

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, UK.

Canonical or classical transient receptor potential 4 and 5 proteins (TRPC4 and TRPC5) assemble as homomers or heteromerize with TRPC1 protein to form functional nonselective cationic channels with high calcium permeability. These channel complexes, TRPC1/4/5, are widely expressed in nervous and cardiovascular systems, also in other human tissues and cell types. It is debatable that TRPC1 protein is able to form a functional ion channel on its own. Read More

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The role of endothelial leak in pulmonary hypertension (2017 Grover Conference Series).

Pulm Circ 2018 Oct-Dec;8(4):2045894018798569. Epub 2018 Aug 20.

1 Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, USA.

The canonical transient receptor potential 4 (TRPC4) protein contributes to the molecular make-up of endothelial store-operated calcium entry channels. Store-operated calcium entry is a prominent mode of calcium influx in endothelium. Store-operated calcium entry channels are activated by inflammatory mediators and growth factors, and in endothelium, this process induces inter-endothelial cell gaps that increase permeability. Read More

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Gα-mediated TRPC4 activation by polycystin-1 contributes to endothelial function via STAT1 activation.

Sci Rep 2018 02 22;8(1):3480. Epub 2018 Feb 22.

Department of Physiology and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul, 110-799, South Korea.

Hypertension and aneurysm are frequently associated with autosomal dominant polycystic kidney disease (ADPKD) caused by polycystin-1 (PC1) mutations, which is closely related to endothelial dysfunction. PC1 is an atypical G-protein-coupled receptor that activates G-proteins by self-cleavage; currently, however, the molecular and cellular mechanisms of the associated intracellular signaling and ion channel activation remain poorly elucidated. Here, we report an activation mechanism of a calcium-permeable canonical transient receptor potential 4 (TRPC4) channel by PC1 and its endothelial function. Read More

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February 2018

Functional expression of calcium-permeable canonical transient receptor potential 4-containing channels promotes migration of medulloblastoma cells.

J Physiol 2017 08 20;595(16):5525-5544. Epub 2017 Jul 20.

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.

Key Points: The proton sensing ovarian cancer G protein coupled receptor 1 (OGR1, aka GPR68) promotes expression of the canonical transient receptor potential channel subunit TRPC4 in normal and transformed cerebellar granule precursor (DAOY) cells. OGR1 and TRPC4 are prominently expressed in healthy cerebellar tissue throughout postnatal development and in primary cerebellar medulloblastoma tissues. Activation of TRPC4-containing channels in DAOY cells, but not non-transformed granule precursor cells, results in prominent increases in [Ca ] and promotes cell motility in wound healing and transwell migration assays. Read More

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Transient receptor potential (TRP) channel function in the reproductive axis.

Cell Calcium 2017 11 3;67:138-147. Epub 2017 May 3.

Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany. Electronic address:

Transient receptor potential (TRP) channels play important functional roles in the signal transduction machinery of hormone-secreting cells and have recently been implicated in reproductive physiology. While expression studies have demonstrated TRP channel expression at all levels of the hypothalamic-pituitary-gonadal (hpg) axis, functional details about TRP channel action at the level of the individual cells controlling reproduction are just beginning to emerge. Canonical TRP (TRPC) channels are prominently expressed in the reproductive center of the neuroendocrine brain, i. Read More

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November 2017

Calcium permeability of transient receptor potential canonical (TRPC) 4 channels measured by TRPC4-GCaMP6s.

Korean J Physiol Pharmacol 2017 Jan 21;21(1):133-140. Epub 2016 Dec 21.

Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.

Conflicting evidence has been obtained regarding whether transient receptor potential cation channels (TRPC) are store-operated channels (SOCs) or receptor-operated channels (ROCs). Moreover, the Ca/Na permeability ratio differs depending on whether the current-voltage (I-V) curve has a doubly rectifying shape or inward rectifying shape. To investigate the calcium permeability of TRPC4 channels, we attached GCaMP6s to TRPC4 and simultaneously measured the current and calcium signals. Read More

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January 2017

Endothelial hyperpermeability in severe pulmonary arterial hypertension: role of store-operated calcium entry.

Am J Physiol Lung Cell Mol Physiol 2016 09 15;311(3):L560-9. Epub 2016 Jul 15.

Department of Physiology and Cell Biology, University of South Alabama, Mobile, Alabama; Department of Internal Medicine, University of South Alabama, Mobile, Alabama; Center for Lung Biology, University of South Alabama, Mobile, Alabama; and

Here, we tested the hypothesis that animals with severe pulmonary arterial hypertension (PAH) display increased sensitivity to vascular permeability induced by activation of store-operated calcium entry. To test this hypothesis, wild-type and transient receptor potential channel 4 (TRPC4) knockout Fischer 344 rats were given a single injection of Semaxanib (SU5416; 20 mg/kg) followed by 3 wk of exposure to hypoxia (10% oxygen) and a return to normoxia (21% oxygen) for an additional 2-3 wk. This Semaxanib/hypoxia/normoxia (i. Read More

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September 2016

Transient Receptor Potential Channel 4 Encodes a Vascular Permeability Defect and High-Frequency Ca(2+) Transients in Severe Pulmonary Arterial Hypertension.

Am J Pathol 2016 06 12;186(6):1701-9. Epub 2016 Apr 12.

Department of Physiology and Cell Biology, University of South Alabama, Mobile, Alabama; Center for Lung Biology, University of South Alabama, Mobile, Alabama; Department of Medicine, University of South Alabama, Mobile, Alabama. Electronic address:

The canonical transient receptor potential channel 4 (TRPC4) comprises an endothelial store-operated Ca(2+) entry channel, and TRPC4 inactivation confers a survival benefit in pulmonary arterial hypertension (PAH). Endothelial Ca(2+) signals mediated by TRPC4 enhance vascular permeability in vitro, but the contribution of TRPC4-dependent Ca(2+) signals to the regulation of endothelial permeability in PAH is poorly understood. We tested the hypothesis that TRPC4 increases vascular permeability and alters the frequency of endothelial Ca(2+) transients in PAH. Read More

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Sodium entry through endothelial store-operated calcium entry channels: regulation by Orai1.

Am J Physiol Cell Physiol 2015 Feb 26;308(4):C277-88. Epub 2014 Nov 26.

Department of Pharmacology, University of South Alabama, Mobile, Alabama; Department of Medicine, University of South Alabama, Mobile, Alabama; and Center for Lung Biology, University of South Alabama, Mobile, Alabama

Orai1 interacts with transient receptor potential protein of the canonical subfamily (TRPC4) and contributes to calcium selectivity of the endothelial cell store-operated calcium entry current (ISOC). Orai1 silencing increases sodium permeability and decreases membrane-associated calcium, although it is not known whether Orai1 is an important determinant of cytosolic sodium transitions. We test the hypothesis that, upon activation of store-operated calcium entry channels, Orai1 is a critical determinant of cytosolic sodium transitions. Read More

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February 2015


Handb Exp Pharmacol 2014 ;222:129-56

Department of Biophysics, Educational and Scientific Centre "Institute of Biology", Taras Shevchenko Kiev National University, Kiev, 03022, Ukraine,

Human canonical transient receptor potential channel 5 (TRPC5) has been cloned from the Xq23 region on chromosome X as a suspect in nonsyndromic mental retardation. TRPC5 is a Ca(2+)-permeable cation channel predominantly expressed in the CNS, including the hippocampus, cerebellum, amygdala, sensory neurons, and retina. It also shows more restricted expression in the periphery, notably in the kidney and cardiovascular system. Read More

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TRPC4- and TRPC4-containing channels.

Handb Exp Pharmacol 2014 ;222:85-128

Pharmakologisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany,

TRPC4 proteins comprise six transmembrane domains, a putative pore-forming region, and an intracellularly located amino- and carboxy-terminus. Among eleven splice variants identified so far, TRPC4α and TRPC4β are the most abundantly expressed and functionally characterized. TRPC4 is expressed in various organs and cell types including the soma and dendrites of numerous types of neurons; the cardiovascular system including endothelial, smooth muscle, and cardiac cells; myometrial and skeletal muscle cells; kidney; and immune cells such as mast cells. Read More

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Activation of TRPC4β by Gαi subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron.

Cell Calcium 2013 Oct 14;54(4):307-19. Epub 2013 Aug 14.

Department of Physiology and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.

The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca(2+)-permeable channels. TRPC channels are activated by stimulation of Gαq-PLC-coupled receptors. Here, we report that TRPC4/TRPC5 can be activated by Gαi. Read More

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October 2013

Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue.

Pharmacol Rep 2013 ;65(3):751-5

National Agri-Food Biotechnology Institute (NABI), SAS Nagar (Mohali)-160071, Punjab, India.

Background: Calcium and its signaling have a role in adipogenesis. Transient Receptor Potential (TRP) channels are non-selective cation channels with a high permeability to calcium.

Methods: In the present study the expression of multiple TRP channels on mouse 3T3-L1 preadipocyte and adipocyte cells, white (WAT) and brown (BAT) adipose tissues was investigated using real time PCR (RT-PCR). Read More

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In pursuit of small molecule chemistry for calcium-permeable non-selective TRPC channels -- mirage or pot of gold?

Br J Pharmacol 2013 Oct;170(3):459-74

School of Chemistry, University of Leeds, Leeds, UK.

The primary purpose of this review is to address the progress towards small molecule modulators of human Transient Receptor Potential Canonical proteins (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7). These proteins generate channels for calcium and sodium ion entry. They are relevant to many mammalian cell types including acinar gland cells, adipocytes, astrocytes, cardiac myocytes, cochlea hair cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, keratinocytes, leukocytes, mast cells, mesangial cells, neurones, osteoblasts, osteoclasts, platelets, podocytes, smooth muscle cells, skeletal muscle and tumour cells. Read More

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October 2013

Wakayama symposium: dependence of corneal epithelial homeostasis on transient receptor potential function.

Ocul Surf 2013 Jan 10;11(1):8-11. Epub 2012 Sep 10.

Department of Biological Sciences, State University of New York, State College of Optometry, New York, NY, USA.

Transient receptor potential (TRP) protein expression in the corneal epithelial layer contributes to the maintenance of tissue transparency. These proteins are members of a superfamily that form nonselective cation channels. This superfamily is a product of 28 different genes that are subdivided into six different subfamilies according to differences in amino acid sequence homology. Read More

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January 2013

Malathion/oxon and lead acetate increase gene expression and protein levels of transient receptor potential canonical channel subunits TRPC1 and TRPC4 in rat endothelial cells of the blood-brain barrier.

Int J Toxicol 2012 Jun;31(3):238-49

Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.

This study examined the effects of malathion and lead on transient receptor potential canonical channel TRPC1/TRPC4 channels in rat brain endothelial cells as a mechanism to explain previously noted blood-brain barrier (BBB) permeability induced by these compounds. Lead, malathion, malaoxon and combinations of these were assessed for protein levels and gene expression of TRPC1/C4 at 2, 4, 8, 16, and 24 hours after exposure. Changes in intracellular free calcium dynamics were also assessed. Read More

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Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel.

Circ Res 2012 May 24;110(11):1435-44. Epub 2012 Apr 24.

Department of Biochemistry and Molecular Biology, University of South Alabama College of Medicine, Mobile, AL 36688, USA. dlcioffi@ usouthal.edu

Rationale: Canonical transient receptor potential 4 (TRPC4) contributes to the molecular composition of a channel encoding for a calcium selective store-operated current, I(SOC), whereas Orai1 critically comprises a channel encoding for the highly selective calcium release activated calcium current, I(CRAC). However, Orai1 may interact with TRPC proteins and influence their activation and permeation characteristics. Endothelium expresses both TRPC4 and Orai1, and it remains unclear as to whether Orai1 interacts with TRPC4 and contributes to calcium permeation through the TPRC4 channel. Read More

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Dependence of spontaneous electrical activity and basal prolactin release on nonselective cation channels in pituitary lactotrophs.

Physiol Res 2012 5;61(3):267-75. Epub 2012 Apr 5.

Section on Cellular Signaling, PDN, NICHD, National Institutes of Health, Bethesda, USA.

All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na(+) with large organic cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na(+) with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Read More

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December 2012

Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes.

J Biol Chem 2012 Jan 8;287(5):3530-40. Epub 2011 Dec 8.

Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians University, 80336 Munich, Germany.

Specific biological roles of the classical transient receptor potential channel 1 (TRPC1) are still largely elusive. To investigate the function of TRPC1 proteins in cell physiology, we studied heterologously expressed TRPC1 channels and found that recombinant TRPC1 subunits do not form functional homomeric channels. Instead, by electrophysiological analysis TRPC1 was shown to form functional heteromeric, receptor-operated channel complexes with TRPC3, -4, -5, -6, and -7 indicating that TRPC1 proteins can co-assemble with all members of the TRPC subfamily. Read More

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January 2012

Impaired Orai1-mediated resting Ca2+ entry reduces the cytosolic [Ca2+] and sarcoplasmic reticulum Ca2+ loading in quiescent junctophilin 1 knock-out myotubes.

J Biol Chem 2010 Dec 11;285(50):39171-9. Epub 2010 Oct 11.

Department of Anesthesiology Perioperative and Pain Medicine, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.

In the absence of store depletion, plasmalemmal Ca(2+) permeability in resting muscle is very low, and its contribution in the maintenance of Ca(2+) homeostasis at rest has not been studied in detail. Junctophilin 1 knock-out myotubes (JP1 KO) have a severe reduction in store-operated Ca(2+) entry, presumably caused by physical alteration of the sarcoplasmic reticulum (SR) and T-tubule junction, leading to disruption of the SR signal sent by Stim1 to activate Orai1. Using JP1 KO myotubes as a model, we assessed the contribution of the Orai1-mediated Ca(2+) entry pathway on overall Ca(2+) homeostasis at rest with no store depletion. Read More

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December 2010

Transient receptor potential channel activation and endothelium-dependent dilation in the systemic circulation.

J Cardiovasc Pharmacol 2011 Feb;57(2):133-9

Department of Medicine, Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Rd Milwaukee, WI 53226, USA.

The endothelium plays a crucial role in the regulation of vascular tone by releasing a number of vasodilator mediators, including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor(s). The production of these mediators is typically initiated by an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in endothelial cells. An essential component of this Ca(2+) signal is the entry of Ca(2+) from the extracellular space through plasma membrane Ca(2+)-permeable channels. Read More

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February 2011

Store-operated Ca(2+) entry is expressed in human endothelial progenitor cells.

Stem Cells Dev 2010 Dec 13;19(12):1967-81. Epub 2010 Sep 13.

Department of Physiology, University of Pavia, Pavia, Italy.

Endothelial progenitor cells (EPCs) may be recruited from the bone marrow to sites of tissue regeneration to sustain neovascularization and reendothelialization after acute vascular injury. This feature makes them particularly suitable for cell-based therapy. In mature endothelium, store-operated Ca(2+) entry (SOCE) is activated following emptying of inositol-1,4,5-trisphosphate-sensitive stores, and controls a wide number of functions, including proliferation, nitric oxide synthesis, and vascular permeability. Read More

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December 2010

TRPV4 channels augment macrophage activation and ventilator-induced lung injury.

Am J Physiol Lung Cell Mol Physiol 2010 Sep 18;299(3):L353-62. Epub 2010 Jun 18.

Department of Physiology, University of South Alabama, Mobile, Alabama 36688, USA.

We have previously implicated transient receptor potential vanilloid 4 (TRPV4) channels and alveolar macrophages in initiating the permeability increase in response to high peak inflation pressure (PIP) ventilation. Alveolar macrophages were harvested from TRPV4(-/-) and TRPV4(+/+) mice and instilled in the lungs of mice of the opposite genotype. Filtration coefficients (K(f)) measured in isolated perfused lungs after ventilation with successive 30-min periods of 9, 25, and 35 cmH(2)O PIP did not significantly increase in lungs from TRPV4(-/-) mice but increased >2. Read More

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September 2010

TRUSS, TNF-R1, and TRPC ion channels synergistically reverse endoplasmic reticulum Ca2+ storage reduction in response to m1 muscarinic acetylcholine receptor signaling.

J Cell Physiol 2010 Nov;225(2):444-53

Department of Pediatrics, National Jewish Health, Denver, Colorado 80206, USA.

Although most signaling responses initiated by tumor necrosis factor-alpha (TNF-alpha) occur in a Ca(2+)-independent fashion, TNF-alpha receptor signaling augments Ca(2+) entry induced by Galpha(q/11) G-protein coupled receptors (GPCRs) in endothelial cells and increases trans-endothelial permeability. The signaling events involved in GPCR-induced Ca(2+) influx have been characterized and involve store-operated Ca(2+) entry facilitated by the Ca(2+) permeable ion channel, transient receptor potential canonical 4 (TRPC4). Little is known about the mechanisms by which TNF-alpha receptor signaling augments GPCR-induced Ca(2+) entry. Read More

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November 2010

Intracellular calcium strongly potentiates agonist-activated TRPC5 channels.

J Gen Physiol 2009 May;133(5):525-46

Howard Hughes Medical Institute, Department of Cardiology and Manton Center for Orphan Disease, Children's Hospital Boston, and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

TRPC5 is a calcium (Ca(2+))-permeable nonselective cation channel expressed in several brain regions, including the hippocampus, cerebellum, and amygdala. Although TRPC5 is activated by receptors coupled to phospholipase C, the precise signaling pathway and modulatory signals remain poorly defined. We find that during continuous agonist activation, heterologously expressed TRPC5 currents are potentiated in a voltage-dependent manner ( approximately 5-fold at positive potentials and approximately 25-fold at negative potentials). Read More

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TRPing on the lung endothelium: calcium channels that regulate barrier function.

Antioxid Redox Signal 2009 Apr;11(4):765-76

Center for Lung Biology, University of South Alabama, Mobile, Alabama 36688, USA.

Rises in cytosolic calcium are sufficient to initiate the retraction of endothelial cell borders and to increase macromolecular permeability. Although endothelial cell biologists have recognized the importance of shifts in cytosolic calcium for several decades, only recently have we gained a rudimentary understanding of the membrane calcium channels that change cell shape. Members of the transient receptor potential family (TRP) are chief among the molecular candidates for permeability-coupled calcium channels. Read More

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Basal calcium entry in retinal pigment epithelial cells is mediated by TRPC channels.

Invest Ophthalmol Vis Sci 2007 Dec;48(12):5767-72

Experimentelle Ophthalmologie, Klinik und Poliklinik für Augenheilkunde, Universitätsklinkikum Hamburg-Eppendorf, Hamburg, Germany.

Purpose: Ca(2+) is a major regulator of cell function. In the retinal pigment epithelium (RPE), intracellular free Ca(2+) concentration ([Ca(2+)](i)) is essential for the maintenance of normal retinal function. Therefore, accurate control of [Ca(2+)](i) is vital in these cells. Read More

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December 2007