SEARCH · PubMed Health

Results for “TRPC6 Cation Channel”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed2003

PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression.

Capacitative Ca(2+) entry (CCE) through store-operated Ca(2+) (SOC) channels plays an important role in returning Ca(2+) to the sarcoplasmic reticulum (SR) and regulating cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)). A rise in [Ca(2+)](cyt) and sufficient Ca(2+) in the SR are required for pulmonary artery smooth muscle cell (PASMC) proliferation. We tested the hypothesis that platelet-derived growth factor (PDGF)-mediated PASMC growth involves upregulation of c-Jun and TRPC6, a transient receptor potential cation channel. In rat PASMC, PDGF (10 ng/ml for 0.5-48 h) phosphorylated signal transducer and activator of transcription (STAT3), increased mRNA and protein levels of c-Jun, and stimulated cell proliferation. PDGF treatment also upregulated TRPC6 expression and augmented CCE, elicited by passive depletion of Ca(2+) from the SR using cyclopiazonic acid. Furthermore, overexpression of c-Jun stimulated TRPC6 expression and CCE amplitude in PASMC. Downregulation of TRPC6 using an antisense oligonucleotide specifically for human TRPC6 decreased CCE and inhibited PDGF-mediated PASMC proliferation. These results suggest that PDGF-mediated PASMC proliferation is associated with c-Jun/STAT3-induced upregulation of TRPC6 expression. The resultant increase in CCE raises [Ca(2+)](cyt), facilitates return of Ca(2+) to the SR, and enhances PASMC growth.

Animals↗

PubMed2002

Transient receptor potential channels regulate myogenic tone of resistance arteries.

Elevation of intravascular pressure causes depolarization and constriction (myogenic tone) of small arteries and arterioles, and this response is a key element in blood flow regulation. However, the nature of pressure-induced depolarization has remained elusive. In the present study, we provide evidence that a transient receptor potential channel (TRPC6) homologue has a major role in this depolarizing response to pressure. Antisense oligodeoxynucleotides to TRPC6 decreased TRPC6 protein expression and greatly attenuated arterial smooth muscle depolarization and constriction caused by elevated pressure in intact cerebral arteries. Suppressing the expression of this channel protein also reduced the current density of a major cation current in resistance artery smooth muscle cells. We propose that TRPC6 channels play an essential role in regulation of myogenic tone.

Animals↗

PubMed2003

Synergism between inositol phosphates and diacylglycerol on native TRPC6-like channels in rabbit portal vein myocytes.

In rabbit portal vein myocytes noradrenaline activates a non-selective cation current (Icat) which involves a transient receptor potential protein (TRPC6). Previously we have shown that the diaylglycerol (DAG) analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulates Icat via a protein kinase C (PKC)-independent mechanism, and in the present study we have investigated the interaction between inositol phosphates (InsPs) and OAG on Icat. With whole-cell recording of Icat from freshly isolated rabbit portal vein myocytes the amplitude and rate of activation of noradrenaline-evoked Icat were much greater than those of OAG-induced Icat. Inclusion of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in the pipette solution did not evoke Icat but greatly potentiated the amplitude and rate of activation of OAG-induced Icat. With isolated outside-out patches Ins(1,4,5)P3 markedly increased the rate of activation and the open probability of OAG-evoked channel activity, with no change in unitary conductance, channel mean open times or burst durations. The effects of Ins(1,4,5)P3 were mimicked by Ins(2,4,5)P3, 3-F-Ins(1,4,5)P3 and Ins(1,4)P2 but not by Ins(1,3,4,5)P4 and the potentiating effects of InsPs were not inhibited by heparin. Therefore it is concluded that both DAG and InsPs are necessary for full activation of Icat by noradrenaline and the effect of InsPs is via a heparin-insensitive mechanism and represents a novel action of InsPs.

Animals↗

PubMed2004

Two types of non-selective cation channel opened by muscarinic stimulation with carbachol in bovine ciliary muscle cells.

In the ciliary muscle, the tonic contraction requires a sustained influx of Ca2+ through the cell membrane. However, little has hitherto been known about the route(s) of Ca2+ influx in this tissue that lacks voltage-gated Ca2+ channels. To identify ion channels as the Ca2+ entry pathway we studied the effects of carbachol (CCh) on freshly isolated bovine ciliary muscle cells by whole-cell voltage clamp. Experiments were carried out using pipettes filled with K+ -free solution containing 100 mm caesium aspartate, 5 mm BAPTA and 180 microm GTP (pH 7.0; the intracellular free Ca2+ concentration, [Ca2+]i = 70 nm). CCh evoked an inward current showing polarity reversal at a holding potential near 0 mV. Analysis of the current noise distinguished two types of non-selective cation channel (NSCCL and NSCCS) with widely different unitary conductances (35 pS and 100 fS). The ratios of the permeabilities to Li+, Na+, Cs+, Mg2+, Ca2+, Sr2+ and Ba2+, estimated by cation replacement procedures, were 0.9: 1.0: 1.5: 0.2: 0.3: 0.4: 0.5 for NSCCL, and 1.0: 1.0: 1.8: 2.5: 2.6: 3.2: 5.0 for NSCCS. NSCCS, but not NSCCL, was strongly inhibited by elevation of [Ca2+]i. Both NSCCL and NSCCS were dose-dependently inhibited by 1-100 microm SKF96365, La3+ and Gd3+, which also inhibited the tonic component of the contraction produced in muscle bundles by CCh without markedly affecting the initial phasic component. NSCCL and/or NSCCS may serve as a major Ca2+ entry pathway required for sustained contraction of the bovine ciliary muscle. RT-PCR experiments in the bovine ciliary muscle (whole tissue) detected mRNAs of several transient receptor potential (TRP) channel homologues (TRPC1, TRPC3, TRPC4 and TRPC6), which are now regarded as possible molecular candidates for receptor-operated cation channels.

Animals↗

PubMed2006

TRPC6 silencing in primary airway smooth muscle cells inhibits protein expression without affecting OAG-induced calcium entry.

TRPC proteins have been described as non-selective cation channels and are thought to be involved in the regulation of Ca(2+) movement in various cells, including airway smooth muscle (ASM) cells. In order to study the role of these channels in ASM cells, transfection of a small interfering RNA (siRNA) designed against the TRPC6 channel was performed in guinea pig primary ASM cells. This specific siRNA was complexed with the new X-TremeGene (X-TG) chemical transfection reagent, whose efficiency and low cytotoxicity were determined by the use of a non-silencing rhodamine-tagged siRNA. It was found that more than 95% of cells were transfected by an optimized protocol. Verification of TRPC6 transcript down-regulation was determined by RT-PCR while Western blot analysis attested to lower protein content in the microsomal fraction. Micro-spectrofluorimetry measurements of control and siRNA-treated cells revealed that lower TRPC6 expression did not affect OAG-induced intracellular Ca(2+) movement. Thus, TRPC6 channels cannot be defined as simple Ca(2+) transporters but more likely as protein complexes supporting monovalent cation conductance in ASM cells. These conductances would in turn facilitate membrane depolarization of high input resistance cells, Ca(2+) channel activation and tone increase. In conclusion, this study defines a valuable model of RNA interference study in primary cultures of ASM cells, eventually allowing for silencing of other target proteins for which no pharmacological modulators are currently available.

Animals↗

PubMed2006

Na+ entry via TRPC6 causes Ca2+ entry via NCX reversal in ATP stimulated smooth muscle cells.

Reversal of the Na+/Ca2+ -exchanger (NCX) has been shown to mediate Ca2+ influx during activation of G-protein linked receptors. Functional coupling between the reverse-mode NCX and the canonical transient receptor potential channels (TRPCs) has been proposed to mediate Ca2+ influx in HEK-293 cells overexpressing TRPC3. In this communication we present evidence for similar functional coupling of NCX to endogenously expressed TRPC6 in rat aorta smooth muscle cells. Selective inhibition of reverse-mode NCX with KB-R7943 and of non-selective cation-channels with SKF-96365 abolished Ca2+ influx in response to agonist stimulation (ATP). Expression of a dominant negative TRPC6 mutant also reduced the Ca2+ influx in proportion to its transfection efficiency. Calyculin A, which is known to disrupt the junctions of the plasma membrane and sarco/endoplasmic reticulum, increased global Na+ elevations and reduced stimulated Ca2+ influx. Together our data provide evidence that localized Na+ elevations are generated by TRPC6 and drive reversal of NCX to mediate Ca2+ influx.

Adenosine Triphosphate↗

PubMed2006

Calcium-sensing receptor stimulation induces nonselective cation channel activation in breast cancer cells.

The calcium-sensing receptor (CaR) is expressed in epithelial ducts of both normal human breast and breast cancer tissue, as well as in the MCF-7 cell line as assessed by immunohistochemistry and Western blot analysis. However, to date, there are no data regarding the transduction pathways of CaR in breast cancer cells. In this study, we show that a CaR agonist, spermine, and increased extracellular Ca(2+) ([Ca(2+)](o)) sequentially activate two inward currents at -80 mV. The first was highly permeable to Ca(2+) and inhibited by 2-aminophenyl borate (2-APB). In contrast, the second was more sensitive to Na(+) and Li(+) than to Ca(2+) and insensitive to 2-APB. Furthermore, intracellular dialysis with high Mg(2+), flufenamic acid or amiloride perfusion was without any effect on the second current. Both currents were inhibited by La(3+). Calcium imaging recordings showed that both [Ca(2+)](o) and spermine induced an increase in intracellular calcium ([Ca(2+)](i)) and that removal of extracellular Ca(2+) or perfusion of 2-APB caused a decline in [Ca(2+)](i). It is well known that stimulation of CaR by an increase in [Ca(2+)](o) or with spermine is associated with activation of phospholipase C (PLC). Inhibition of PLC reduced the [Ca(2+)](o)-stimulated [Ca(2+)](i) increase. Lastly, reverse-transcriptase polymerase chain reaction showed that MCF-7 cells expressed canonical transient receptor potential (TRPCs) channels. Our results suggest that, in MCF-7 cells, CaR is functionally coupled to Ca(2+)-permeable cationic TRPCs, for which TRPC1 and TRPC6 are the most likely candidates for the highly selective Ca(2+) current. Moreover, the pharmacology of the second Na(+) current excludes the involvement of the more selective Na(+) transient receptor potential melastatin (TRPM4 and TRPM5) and the classical epithelial Na(+ )channels.

Animals↗

PubMed2004

Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+ channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension.

Chronic hypoxic pulmonary hypertension is associated with profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Recent studies show that transient receptor potential (TRPC) genes, which encode store-operated and receptor-operated cation channels, play important roles in Ca(2+) regulation and cell proliferation. However, the influence of chronic hypoxia on TRPC channels has not been determined. Here we compared TRPC expression, and store- and receptor-operated Ca(2+) entries in PASMCs of normoxic and chronic hypoxic rats. Reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunostaining showed consistently that TRPC1, TRPC3, and TRPC6 were expressed in intralobar pulmonary arteries (PAs) and PASMCs. Application of 1-oleoyl-2-acetyl-sn-glycerol (OAG) to directly activate receptor-operated channels, or thapsigargin to deplete Ca(2+) stores, caused dramatic increase in cation entry measured by Mn(2+) quenching of fura-2 and by Ca(2+) transients. OAG-induced responses were approximately 700-fold more resistant to La(3+) inhibition than thapsigargin-induced responses. siRNA knockdown of TRPC1 and TRPC6 specifically attenuated thapsigargin- and OAG-induced cation entries, respectively, indicating that TRPC1 mediates store-operated entry and TRPC6 mediates receptor-operated entry. In hypoxic PAs, there were 2- to 3-fold increases in TRPC1 and TRPC6 expression. They were accompanied by significant increases in basal, OAG-induced, and thapsigargin-induced cation entries in hypoxic PASMCs. Moreover, removal of Ca(2+) or inhibition of store-operated Ca(2+) entry with La(3+) and SK&F-96365 reversed the elevated basal [Ca(2+)](i) in PASMCs and vascular tone in PAs of chronic hypoxic animals, but nifedipine had minimal effects. Our results for the first time to our knowledge show that both store- and receptor-operated channels of PASMCs are upregulated by chronic hypoxia and contribute to the enhanced vascular tone in hypoxic pulmonary hypertension.

Animals↗

PubMed2006

TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling.

The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of beta-myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling.

Animals↗

PubMed2007

TRP channels in platelet function.

Ca2+ entry forms an essential component of platelet activation; however, the mechanisms associated with this process are not understood. Ca2+ entry upon receptor activation occurs as a consequence of intracellular store depletion (referred to as store-operated Ca2+ entry or SOCE), a direct action of second messengers on cation entry channels or the direct occupancy of a ligand-gated P2(Xi) receptor. The molecular identity of the SOCE channel has yet to be established. Transient receptor potential (TRP) proteins are candidate cation entry channels and are classified into a number of closely related subfamilies including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin) and TRPML (mucolipins). From the TRPC family, platelets have been shown to express TRPC6 and TRPC1, and are likely to express other TRPC and other TRP members. TRPC6 is suggested to be involved with receptor-activated, diacyl-glycerol-mediated cation entry. TRPC1 has been suggested to be involved with SOCE, though many of the suggested mechanisms remain controversial. As no single TRP channel has the properties described for SOCE in platelets, it is likely that it is composed of a heteromeric association of TRP and related subunits, some of which may be present in intracellular compartments in the resting cell.

Animals↗

PubMed2005

Mechanism of inhibition of TRPC cation channels by 2-aminoethoxydiphenylborane.

We investigated the actions of the organoborane, 2-aminoethoxydiphenylborane (2APB), on Ca2+ signaling in wild-type human embryonic kidney (HEK) 293 cells and in HEK293 cells stably expressing canonical transient receptor potential (TRPC) channels. Previous reports have suggested that 2APB inhibits agonist activation of TRPC channels because of its ability to act as a membrane-permeant inhibitor of inositol 1,4,5-trisphosphate (IP3) receptors. 2APB was specifically said to inhibit TRPC3 channels when activated through a phospholipase C-linked receptor but not when activated more directly by a synthetic diacylglycerol, oleyl-acetyl-glycerol (OAG) [Science (Wash DC) 287:1647-1651, 2000]. However, we subsequently reported that IP3 does not activate TRPC3; rather the mechanism of activation by phospholipase C-linked receptors seemed to result from diacylglycerol [J Biol Chem 278:16244-16252, 2003]. Thus, the current study was carried out to address the mechanism of action of 2APB in inhibiting TRPC channels. We found that, although the release of Ca2+ by a muscarinic agonist was reduced by high concentrations of 2APB, this effect was indistinguishable from that seen when stores were discharged by thapsigargin, which does not involve IP3 receptors. This indicates that 2APB is incapable of significant inhibition of IP3 receptors when applied to intact cells. We found that 2APB partially inhibits divalent cation entry in cells expressing TRPC3, TRPC6, or TRPC7 and that this partial inhibition was observed whether the channels were activated by a muscarinic agonist or by OAG. Thus, as concluded for store-operated channels, 2APB seems to inhibit TRPC channels by a direct mechanism not involving IP3 receptors.

Boron Compounds↗

PubMed2002

TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia.

Tachykinins depolarize guinea pig intracardiac neurons by activating nonselective cationic channels. Recently, members of the transient receptor potential family of membrane channels (TRPC) have been implicated in the generation of G protein-coupled receptor-activated nonselective cationic currents. We have investigated whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited immunoreactivity to TRPC6. After culture of cardiac ganglia whole-mount explants for 72 hours, the TRPC6-IR fiber networks were absent. Therefore, the TRPC6-IR fibers were derived from sources extrinsic to the heart. A small percentage ( approximately 3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity in control preparations, and the percentage of cells exhibiting TRPC6 immunoreactivity was not changed following explant culture for 72 hours. The few intrinsic TRPC6-IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of TRPC6-IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The TRPC6-IR fibers were not immunoreactive for choline acetyltransferase, tyrosine hydroxylase, or substance P. However, the TRPC6-IR fibers exhibited immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6-IR fibers within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that also contain NOS. We found, in support of this conclusion, that TRPC6-IR cells were also present in sections of nodose ganglia.

Animals↗

PubMed2004

Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP.

Throughout the body there are smooth muscle cells controlling a myriad of tubes and reservoirs. The cells show enormous diversity and complexity compounded by a plasticity that is critical in physiology and disease. Over the past quarter of a century we have seen that smooth muscle cells contain--as part of a gamut of ion-handling mechanisms--a family of cationic channels with significant permeability to calcium, potassium and sodium. Several of these channels are sensors of calcium store depletion, G-protein-coupled receptor activation, membrane stretch, intracellular Ca2+, pH, phospholipid signals and other factors. Progress in understanding the channels has, however, been hampered by a paucity of specific pharmacological agents and difficulty in identifying the underlying genes. In this review we summarize current knowledge of these smooth muscle cationic channels and evaluate the hypothesis that the underlying genes are homologues of Drosophila TRP (transient receptor potential). Direct evidence exists for roles of TRPC1, TRPC4/5, TRPC6, TRPV2, TRPP1 and TRPP2, and more are likely to be added soon. Some of these TRP proteins respond to a multiplicity of activation signals--promiscuity of gating that could enable a variety of context-dependent functions. We would seem to be witnessing the first phase of the molecular delineation of these cationic channels, something that should prove a leap forward for strategies aimed at developing new selective pharmacological agents and understanding the activation mechanisms and functions of these channels in physiological systems.

Amino Acid Sequence↗

PubMedDate not supplied

Role and regulation of TRP channels in neutrophil granulocytes.

Members of the transient receptor potential (TRP) family for which mRNA can be demonstrated in neutrophil granulocytes with RT-PCR include TRPC6 (as only "short" TRP), TRPM2, TRPV1, TRPV2, TRPV5 and TRPV6. When these are analyzed in heterologous overexpression experiments, TRPM2 is the only cation channel with characteristic properties that can be used as fingerprint to provide functional evidence for its expression in neutrophil granulocytes. As cells transfected with TRPM2, neutrophil granulocytes display non-selective cation currents and typical channel activity evoked by intracellular ADP-ribose and NAD. Thus, stimulation of TRPM2 is likely to occur after activation of CD38 (producing ADP-ribose) and during the oxidative burst (enhancing the NAD concentration). This novel mode of cation entry regulation may be of particular importance for the response of granulocytes to chemoattractants. TRPV6 is a likely but not exclusive candidate as subunit of the channels mediating store-operated Ca2+ entry (SOCE). Evidence for SOCE in granulocytes has been presented with the fura-2 technique but not with electrophysiological methods although Ca2+-selective store-operated currents can be demonstrated in HL-60 cells, a cell culture model of neutrophil granulocytes.

Adenosine Diphosphate Ribose↗

PubMed2003

Distribution of transient receptor potential channels in the rat carotid chemosensory pathway.

Glomus cells in the carotid body respond to decreases in oxygen tension of the blood and transmit this sensory information in the carotid sinus nerve to the brain via neurons in the petrosal ganglion. G-protein-coupled membrane receptors linked to phospholipase C may play an important role in this response through the activation of the cation channels formed by the transient receptor potential (TRP) proteins. In the present study, expression of TRPC proteins in the rat carotid body and petrosal ganglion was examined using immunohistochemical techniques. TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7 were present in neurons throughout the ganglion. TRPC1 was expressed in only 28% of petrosal neurons, and of this population, 45% were tyrosine hydroxylase (TH)-positive, accounting for essentially all the TH-expressing neurons in the ganglion. Because TH-positive neurons project to the carotid body, this result suggests that TRPC1 is selectively associated with the chemosensory pathway. Confocal images through the carotid body showed that TRPC1/3/4/5/6 proteins localize to the carotid sinus nerve fibers, some of which were immunoreactive to an anti-neurofilament (NF) antibody cocktail. TRPC1 and TRPC3 were present in both NF-positive and NF-negative fibers, whereas TPRC4, TRPC5, and TRPC6 expression was primarily localized to NF-negative fibers. Only TRPC1 and TRPC4 were localized in the afferent nerve terminals that encircle individual glomus cells. TRPC7 was not expressed in sensory fibers. All the TRPC proteins studied were present in type I glomus cells. Although their role as receptor-activated cation channels in the chemosensory pathway is yet to be established, the presence of TRPC channels in glomus cells and sensory nerves of the carotid body suggests a role in facilitating and/or sustaining the hypoxic response.

Animals↗

PubMed2005

The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance.

Among the "classical" or "canonical" transient receptor potential (TRPC) family, the TRPC3, -6, and -7 channels share 75% amino acid identity and are gated by exposure to diacylglycerol. TRPC3, TRPC6, and TRPC7 interact physically and coassemble to form functional tetrameric channels. This review focuses on the TRPC3/6/7 subfamily and describes their functional properties and regulation as homomers obtained from overexpression studies in cell lines. It also summarizes their heteromultimerization potential in vitro and in vivo and presents initial data concerning their physiological functions analyzed in isolated tissues with downregulated channel activity and gene-deficient mouse models.

Animals↗

PubMed2003

Evidence for the expression of transient receptor potential proteins in guinea pig airway smooth muscle cells.

OBJECTIVE: The present study investigates the expression of transient receptor potential (TRPC) proteins in airway smooth muscle (ASM) cells in order to determine whether these proteins may be candidate molecular counterparts of plasma membrane Ca2+-permeable channels involved in the contraction of ASM. METHODS: Expression of TRPC mRNA was detected using specific primers and RT-PCR. Expression of the TRPC1, TRPC3 and TRPC6 proteins was detected using antibodies in immunoprecipitation and Western blot. RESULTS: Guinea pig ASM cells exhibited thapsigargin- and acetylcholine-initiated Ca2+ inflow but none by 1-oleoyl-2-acetyl-sn-glycerol. mRNA encoding each of the TRPC1 to TRPC6 proteins was detected in ASM cells. mRNA encoding TRPC1, TRPC3, TRPC4 and TRPC6 was detected in ASM cells at a concentration approximately equivalent to that in guinea pig brain. mRNA encoding TRPC2 and TRPC5 was more abundant in ASM cells than in brain. The TRPC1 protein, but not the TRPC3 or TRPC6 proteins, was detected in extracts of ASM cells, while all three proteins were detected in brain. CONCLUSION: The results provide evidence for a low level of expression of the TRPC1 to TRPC6 proteins in ASM cells. These proteins may function as store-operated Ca2+ and/or second messenger-activated non-selective cation channels in ASM cells.

Airway Resistance↗

PubMed2007

TRPC7.

Canonical transient receptor potential7 (TRPC7) is the seventh identified member of the mammalian TRPC channel family, comprising nonselective cation channels activated through the phospholipase C (PLC) signaling pathway. TRPC7 is directly activated by diacylglycerol (DAG), one of the PLC products, having high sequence homologywith TRPC3 and TRPC6, which are also activated by DAG. TRPC7 shows unique properties of activation, such as constitutive activity and susceptibility to negative regulation by extracellular Ca2+. Although the physiological importance of TRPC7 in the native environment remains elusive, TRPC7 would play important roles in Ca2+ signaling pathway through these characteristic features.

Animals↗