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Results for “Transient Receptor Potential Channels”

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PubMed2006

TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis.

Salsolinol, an endogenous neurotoxin, may be involved in the pathogenesis of Parkinson's disease. In this study, we sought to determine whether salsolinol-induced cytotoxicity in SH-SY5Y human neuroblastoma cells, a cloned cell line which expresses dopaminergic activity, could be prevented by overexpressing a Ca(2+) channel, transient receptor potential (TRPC1) protein. Exposure of SH-SY5Y cells to 500 microM salsolinol for 12 h resulted in a significant decrease in thapsigargin or carbachol-mediated Ca(2+) influx. Consistent with these results, SH-SY5Y cells treated with salsolinol showed approximately 60% reduction in TRPC1 protein levels. Confocal microscopy also showed that SH-SY5Y cells treated with salsolinol had a significant decrease in the plasma membrane staining of the TRPC1 protein. Interestingly, overexpression of TRPC1 increases TRPC1 protein levels and also protected SH-SY5Y neuroblastoma cells against salsolinol-mediated cytotoxicity as determined by 3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The protective effect of TRPC1 was blocked by the addition of TRPC1 blockers lanthanum, or 2APB. Activation of TRPC1 protein by either thapsigargin or carbachol further protected SH-SY5Y cells from salsolinol treatments. Staining of SH-SY5Y cells with an apoptotic marker (YO-PRO-1) showed that TRPC1 protein protects against apoptosis. Furthermore, TRPC1 overexpression also inhibited cytochrome c release and decreased BAX protein levels required for apoptosis. Taken together, these findings suggest that the reduction in cell surface TRPC1 protein expression in response to salsolinol may be a contributory factor in cellular toxicity of the dopaminergic neurons. Furthermore, overexpression of TRPC1 could inhibit apoptotic complex thereby increasing neuronal cell survivability in Parkinson's disease.

Apoptosis↗

PubMed2002

Electronegative electroretinogram in mucolipidosis IV.

OBJECTIVE: To demonstrate the progression of electroretinographic (ERG) findings in mucolipidosis IV. METHODS: Two patients with mucolipidosis IV were examined clinically and their condition was followed up for ophthalmic manifestations of the disease. Electroretinograms were performed on both patients, and conjunctival biopsy specimens were analyzed for characteristic ultrastructural inclusion bodies using light and electron microscopy. Genomic DNA isolated from peripheral blood was screened for 2 major founder mutations in the ML4 gene using polymerase chain reaction and restriction fragment length polymorphism analyses. Haplotypes were confirmed by automated sequencing of polymerase chain reaction products. RESULTS: In patient 1, an ERG obtained at 12 months of age showed mildly subnormal amplitude of rod-mediated and cone-mediated responses and significantly prolonged rod and cone b-wave implicit times. An ERG obtained when the patient was 6.6 years old disclosed marked progression with greater loss of b-wave than a-wave responses to rod-and-cone-mediated activity. Scotopic ERG at the highest intensity was electronegative in configuration. In patient 2, ERG showed minimal rod-mediated responses, severely subnormal cone-mediated responses, and prolonged cone b-wave implicit times. Again, electronegative configuration of the scotopic bright flash response indicated greater disturbance of b-wave generators. CONCLUSIONS: Novel ERG findings in 2 cases of mucolipidosis IV are reported with associated clinical courses, histopathologic abnormality, and genetic studies. In both cases ERGs demonstrate an electronegative configuration, suggesting that the primary retinal disturbance in mucolipidosis IV may occur at or proximal to the photoreceptor terminals.

Child↗

PubMed2001

Sexual dimorphism and developmental expression of signal-transduction machinery in the vomeronasal organ.

We have explored the use of a new model to study the transduction of chemosignals in the vomeronasal organ (VNO), for which the functional pathway for chemical communication is incompletely understood. Because putative vomeronasal receptors in mammalian and other vertebrate models belong to the superfamily of G-protein-coupled receptors, the objective of the present study was to define which G-protein subunits were present in the VNO of Sternotherus odoratus (stinkpot or musk turtle) in order to provide directionality for future functional studies of the downstream signaling cascades. The turtle vomeronasal epithelium (VNE) was found to contain the G-proteins G(beta) and G(alphail-3) at the microvillar layer, the presumed site of signal tranduction in these neurons, as evidenced by immunocytochemical techniques. G(alphao) labeled the axon bundles in the VNE and the somata of the vomeronasal sensory neurons but not the microvillar layer. Densitometric analysis of Western blots indicated that the VNO from females contained greater concentrations of G(alphai1-3) compared with males. Sexually immature (juvenile) turtles showed intense immunolabeling for all three subunits (G(beta), G(alphai1-3), and G(alphao)) in the axon bundles and an absence of labeling in the microvillar layer. Another putative signaling component found in the microvilli of mammalian VNO, transient receptor potential channel, was also immunoreactive in S. odoratus in a gender-specific manner, as quantified by Western blot analysis. These data demonstrate the utility of Sternotherus for discerning the functional signal transduction machinery in the VNO and may suggest that gender and developmental differences in effector proteins or cellular signaling components may be used to activate sex-specific behaviors.

Aging↗

PubMed2004

Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system: Implications for regulatory activity within the hypothalamic-pituitary-adrenal axis.

Transient receptor potential channel proteins (TRPs) constitute a steadily growing family of ion channels with a range of purported functions. It has been demonstrated that TRPV2 is activated by moderate thermal stimuli and, in the rat, is expressed in medium to large diameter dorsal root ganglion neurons. In this study, antisera specific for the human TRPV2 homologue were raised and characterized for immunohistochemical use. Subsequently, thorough investigation was made of the localization of this cation channel in the macaque primate brain. TRPV2-immunoreactive material was highly restrictively localized to hypothalamic paraventricular, suprachiasmatic, and supraoptic nuclei. Confocal double- and triple-labeling studies demonstrated that TRPV2 immunoreactivity is preferentially localized to oxytocinergic and vasopressinergic neurons. Few, if any, cells in these regions expressed TRPV2 immunoreactivity in the absence of oxytocin immunoreactivity or vasopressin immunoreactivity. Expression in the paraventricular and supraoptic nuclei suggests that TRPV2 is likely to play a fundamental role in mediating cation transport in neurohypophysial neurons. TRPV2 has been shown to be translocated upon cell activation and neurons expressing TRPV2 immunoreactivity in vivo are among those known to engage in sporadic, intense activity. Taken together, these data suggest that this channel may play a vital role in mediating physiological activities associated with oxytocin and vasopressin release such as parturition, lactation, and diuresis. These data may also implicate the involvement of TRPV2 in disorders of the hypothalamic-pituitary-adrenal axis, including anxiety, depression, hypertension, and preterm labor.

Animals↗

PubMed2001

Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.

The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative, recessive, lysosomal storage disorder. The disease is found in relatively high frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of the MLIV alleles in this population [Bargal et al., 2000]. In this report we complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA were available to us. Four novel mutations were identified in the MCOLN1 gene of severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and an 11-bp insertion in exon 12. The nonsense mutation (R322X) was identified in two unrelated patients with different haplotypes in the MCOLN1 chromosomal region, indicating a mutation hotspot in this CpG site. An in-frame deletion (F408del) was identified in a patient with unusual mild psychomotor retardation. The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100. A preferred nucleotide numbering system for MCOLN1 mutations is presented and the issue of a screening program for the detection of high-risk families in the Jewish Ashkenazi population is discussed.

Codon, Nonsense↗

PubMed2004

Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV.

A patient with mucolipidosis-IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 (MTND5) from her mother that was inserted in-frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236_237ins93). This alteration abolished proper splicing of MCOLN1. The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense-mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models.

Base Sequence↗

PubMed2005

The frequency of mucolipidosis type IV in the Ashkenazi Jewish population and the identification of 3 novel MCOLN1 mutations.

Mucolipidosis type IV (MLIV) is a neurodegenerative lysosomal storage disorder that occurs in an increased frequency in the Ashkenazi Jewish (AJ) population. The frequency of the disease in this population has been established by the testing of 66,749 AJ subjects in the Dor Yeshorim program, a unique premarital population-screening program designed for the Orthodox Jewish community. A carrier rate of 0.0104 (95% C.I 0.0097-0.011) was found. The distribution of the 2 AJ founder mutations, namely, c.416-2A>G and c.1_788del, was determined to be 78.15% and 21.85%, respectively. Three novel mutations were identified in non-Jewish MLIV patients, a missense mutation c.1207C>T, p.Arg403Cys; a 2bp deletion, c.302_303delTC; and a nonsense, c.235C>T, Gln79X.

Base Sequence↗

PubMed2007

Autonomous contractile activity in the isolated rat bladder is modulated by a TRPV1 dependent mechanism.

AIMS: Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient receptor potential channel 1 (TRPV1), is known for its beneficial effects on neurogenic detrusor overactivity. The mainstream rationale for its use is the desensitization of TRPV1 on sensory bladder afferents. However, recent findings showed that TRPV1 is present in other cell types in the bladder. To eliminate the effects of RTX on spinal and central neural circuits, we investigated autonomous contractility in normal and neurogenic rat bladders after treatment with RTX. METHODS: Female Wistar rats were made paraplegic at vertebral level T8-T9. Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM) and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. Effects on contractile parameters of intravesical volume load, the non-selective muscarinic receptor agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in both groups. RESULTS: In RTX-treated normal bladders we found shorter contractions with higher amplitude than in control bladders (P < 0.05). In RTX-treated neurogenic bladders the amplitude and duration of autonomous contractions were increased compared with controls (P < 0.05). Furthermore RTX induced an increased response to CA and to ES (P < 0.05). CONCLUSIONS: RTX significantly affected the properties of autonomous bladder contractile activity. This provides evidence for local effects of RTX on bladder contractile activity, which are not mediated by afferent neural pathways and which may contribute to the beneficial effects on detrusor overactivity. TRPV1 and TRPV1(+) cells seem to play an important role in (autonomous) bladder contractility.

Animals↗

PubMed2000

Identification and characterization of a novel polycystin family member, polycystin-L2, in mouse and human: sequence, expression, alternative splicing, and chromosomal localization.

Polycystins-1, -2, -L, and -REJ are the four known members of the polycystin family of proteins. In this study, we describe a fifth member of the family, polycystin-L2, encoded by PKD2L2 in human and Pkd2l2 in mouse. Full-length cDNA sequences for both mouse and human polycystin-L2 were obtained from testis cDNA. Sequence analysis predicts that the mouse and human polycystin-L2 proteins consist of 621 and 624 amino acid residues, respectively. Polycystin-L2 has significant homology with polycystins-L and -2, with similarities of 58 and 59%, respectively. Both human and murine polycystin-L2 proteins are predicted to have seven putative transmembrane (TM) domains, and, by comparison with transient receptor potential channels, the six carboxyl-terminal TM domains are likely to constitute an ion channel subunit. Northern blot analysis indicated that mouse Pkd2l2 has an abundant approximately 2.5-kb transcript in testis and an approximately 2.2-kb transcript in heart. RT-PCR analysis showed that the full-length transcript is expressed in human brain, kidney, testis, and HepG2 cells, and there are three alternatively spliced variants that were differentially expressed. PKD2L2 consists of 17 exons spanning approximately 50 kb of genomic DNA. PKD2L2 was mapped to human chromosome 5q31 and Pkd2l2 to mouse chromosome 18 in band C.

Alternative Splicing↗

PubMed2007

TRPC2: molecular biology and functional importance.

TRPC (canonical transient receptor potential) channels are the closest mammalian homologs of Drosophila TRP and TRP-like channels. TRPCs are rather nonselective Ca2+ permeable cation channels and affect cell functions through their ability to mediate Ca2+ entry into cells and their action to collapse the plasma membrane potentials. In neurons the latter function leads to action potentials. The mammalian genome codes for seven TRPCs of which TRPC2 is the largest with the most restricted pattern of expression and has several alternatively spliced variants. Expressed in model cells, TRPC2 mediates both receptor- and store depletion-triggered Ca2+ entry. TRPC2 is unique among TRPCs in that its complete gene has been lost from the Old World monkey and human genomes, in which its remnants constitute a pseudogene. Physiological roles for TRPC2 have been studied in mature sperm and the vomeronasal sensory system. In sperm, TRPC2 is activated by the sperm's interaction with the oocyte's zona pellucida, leading to entry of Ca2+ and activation of the acrosome reaction. In the vomeronasal sensory organ (VNO), TRPC2 was found to constitute the transduction channel activated through signaling cascade initiated by the interaction of pheromones with V1R and V2R G protein-coupled receptors on the dendrites of the sensory neurons. V1Rs and V2Rs, the latter working in conjunction with class I MHC molecules, activate G(i)- and G(o)-type G proteins which in turn trigger activation of TRPC2, initiating an axon potential that travels to the axonal terminals. The signal is then projected to the glomeruli of the auxiliary olfactory bulb from where it is carried first to the amygdala and then to higher cortical cognition centers. Immunocytochemistry and gene deletion studies have shown that (1) the V2R-G(o)-MHCIb-beta2m pathway mediates male aggressive behavior in response to pheromones; (2) the V1R-G(i2) pathway mediates mating partner recognition, and (3) these differences have an anatomical correlate in that these functional components are located in anatomically distinct compartments of the VNO. Interestingly, these anatomically segregated signaling pathways use a common transduction channel, TRPC2.

Acrosome Reaction↗

PubMed2003

TRPs make sense.

Drosophila flies with the trp mutation exhibit impaired vision due to the lack of a specific Ca2+ influx pathway in the photoreceptors. The identification of the trp gene product as a Ca2+-permeable ion channel and the search for TRP homologues in flies, worms and mammals has opened the way to the discovery of a whole superfamily of cation channels, baptized TRP channels. In contrast to voltage-gated K+, Na+, or Ca2+ channels, with whom they share their transmembrane architecture, TRP channels are not activated by voltage but by a variety of signals including intra- and extracellular ligands, Ca2+-store depletion and mechanical or thermal stress. Due to the promiscuity of these gating mechanisms, TRP channels are privileged candidates as primary sensing molecules for the recognition and integration of physical and chemical signals from the environment. In this review we discuss recent evidence that implicates members of the TRP superfamily in sensory signal transduction.

Animals↗

PubMed2004

Mucolipin 1: endocytosis and cation channel--a review.

Mucolipidosis type IV (MLIV) is a neurodegenerative, recessive, lysosomal storage disorder characterized by psychomotor retardation and visual impairment due to various ophthalmologic abnormalities. MLIV is found in relatively high frequency in the Ashkenazi Jewish population. The disease is caused by mutations in the gene MCOLN1, which encodes the protein mucolipin 1 (MLN1), a member of the mucolipins family. MLN1 is a non-specific cation channel, and its putative structure attributes it to the TRP superfamily; thus, the gene is also referred as TRPML1. Over 16 MLIV-causing mutations, including two founder mutations in the Ashkenazi population, have been identified hitherto. Atypical increased lysosomal storage in MLIV is present in the cells of all patients. This accumulation is caused by an abnormal endocytosis process of the membrane components to late endosomes to the lysosomes, resulting in an apparent block in the traffic process in pre-lysosomal vacuoles with intraluminal pH of >5.0. MLN1 was localized in cultured cells to late endosomes and lysosomes. The exact function of this cation channel in the late stages of lysosomal maintenance is currently under study.

Endocytosis↗

PubMed2005

Physiological mechanisms of TRPC activation.

TRPC (canonical transient receptor potential) channels are vertebrate homologs of the Drosophila photoreceptor channel, TRP. Considerable research has been brought to bear on the seven members of this family, especially with regard to their possible role in calcium entry. Unfortunately, the current literature presents a confusing picture, with different laboratories producing widely differing results and interpretations. It appears that ectopically expressed TRPC channels can be activated by phospholipase C products (generally, diacylglycerols), by stimulation of trafficking to the plasma membrane, or by depletion of intracellular Ca(2+) stores. Here, I discuss the possibility that these diverse experimental findings arise because TRPC channels can, under both experimental as well as physiological conditions, be activated in three distinct ways, possibly depending on their subunit composition and/or signaling complex environment. The TRPCs may be unique among ion-channel subunit families in being able to participate in the assembly and function of multiple types of physiologically important ion channels.

Animals↗

PubMed2006

The bladder epithelium and overactive bladder: what we know.

Although the urothelium has been traditionally thought of as a passive barrier between urine and detrusor muscle, new studies have shown that the urothelium is a highly specialized structure involved in antigen presentation, micturition reflex, metabolic secretion, inflammatory regulation, and sensory afferent functioning. Data from several laboratories have shown that the urothelium can respond to thermal, mechanical, and chemical stimuli. The earlier findings (activation of urothelial transient receptor potential channel vanilloid 1 producing the second messenger nitric oxide, which in turn triggers suburothelial sensory nerves) demonstrate how the urothelium acts as a transducer, releasing chemicals that target adjacent bladder cells and sensory neurons. We now know that bladder urothelium acts also as a transducer whereby afferent neurons, via urothelial mechanoafferent transduction, are involved in the micturition process and the pathogenesis of bladder disorders. This paper highlights the important role that the urothelium has in bladder pathophysiology.

Humans↗

PubMed2004

Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV.

Most of the membrane trafficking phenomena including those involving the interactions between endosomes and lysosomes are regulated by changes in intracellular Ca2+ (Cai). These processes are disturbed in some types of mucolipidoses and other lysosomal storage disorders, such as mucolipidosis IV (MLIV), a neurological disorder that usually presents during the first year of life with blindness, cognitive impairment, and psychomotor delays. It is caused by mutations in MCOLN1, the gene encoding mucolipin-1 (MLN1), which we have recently established to represent a Ca2+-permeable cation channel that is transiently modulated by changes in Cai. The cells of MLIV patients contain enlarged lysosomes that are likely associated with abnormal sorting and trafficking of these and related organelles. We studied fibroblasts from MLIV patients and found disturbed Ca2+ signaling and large acidic organelles such as late endosomes and lysosomes (LEL) with altered cellular localization in these cells. The fusion between LEL vesicles in these cells was defective. This is a Ca2+-dependent process related to signaling pathways involved in regulation of Ca2+ homeostasis and trafficking. The MLN1 channels could play a key role in Ca2+ release from LEL vesicles, which triggers the fusion and trafficking of these organelles. The characterization of this MLN1-mediated Ca2+-dependent process should provide new insights into the pathophysiological mechanisms that lead to the development of MLIV and other mucolipidoses associated with similar disturbances in membrane trafficking.

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

Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex.

OBJECTIVE: Members of the classical transient receptor potential protein (TRPC) family are considered as key components of phospholipase C (PLC)-dependent Ca2+ signaling. Previous results obtained in the HEK 293 expression system suggested a physical and functional coupling of TRPC3 to the cardiac-type Na+/Ca2+ exchanger, NCX1 (sodium calcium exchanger 1). This study was designed to test for expression of TRPC3 (transient receptor potential channel 3) and for the existence of a native TRPC3/NCX1 signaling complex in rat cardiac myocytes. METHODS: Protein expression and cellular distribution were determined by Western blot and immunocytochemistry. Protein-protein interactions were investigated by reciprocal co-immunoprecipitation and glutathione S-transferase (GST)-pulldown experiments. Recruitment of protein complexes into the plasma membrane was assayed by surface biotinylation. The functional role of TRPC3 was investigated by fluorimetric recording of angiotensin II-induced calcium signals employing a dominant negative knockdown strategy. RESULTS: TRPC3 immunoreactivity was observed in surface plasma membrane regions and in an intracellular membrane system. Co-immunolabeling of TRPC3 and NCX1 indicated significant co-localization of the two proteins. Both co-immunoprecipitation and GST-pulldown experiments demonstrated association of TRPC3 with NCX1. PLC stimulation was found to trigger NCX-mediated Ca2+ entry, which was dependent on TRPC3-mediated Na+ loading of myocytes. This NCX-mediated Ca2+ signaling was significantly suppressed by expression of a dominant negative fragment of TRPC3. PLC stimulation was associated with increased membrane presentation of both TRPC3 and NCX1. CONCLUSION: These results suggest a PLC-dependent recruitment of a TRPC3-NCX1 complex into the plasma membrane as a pivotal mechanism for the control of cardiac Ca2+ homeostasis.

Animals↗

PubMed2006

Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F.

The melastatin-related transient receptor potential channel TRPM2 is a Ca(2+)-permeable channel that is activated by H(2)O(2), and the Ca(2+) influx through TRPM2 mediates cell death. However, the responsible oxidants for TRPM2 activation remain to be identified. In the present study, we investigated the involvement of hydroxyl radical on TRPM2 activation in TRPM2-expressing HEK293 cells and the rat beta-cell line RIN-5F. In both cell types, H(2)O(2) induced Ca(2+) influx in a concentration-dependent manner. However, the addition of hydroxyl radical, which was produced by mixing FeSO(4) and H(2)O(2), to the cells, did not increase intracellular Ca(2+) concentration. Interestingly, when H(2)O(2) was added to the cells under intracellular Fe(2+)-accumulated conditions, Ca(2+) influx was markedly enhanced compared to H(2)O(2) alone. In addition, the H(2)O(2)-induced Ca(2+) influx was reduced by hydroxyl radical scavengers and an iron chelator. Under intracellular Fe(2+)-accumulated conditions, H(2)O(2)-induced RIN-5F cell death through TRPM2 activation was also markedly enhanced. Hydroxyl radical scavengers and an iron chelator suppressed the RIN-5F cell death by H(2)O(2). These results strongly suggest that the intracellular hydroxyl radical plays a key role in the activation of TRPM2 during H(2)O(2) treatment, and TRPM2 activation mediated by hydroxyl radical is implicated in H(2)O(2)-induced cell death in the beta-cell line RIN-5F.

Adenosine Triphosphate↗