Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators

Karashima, Yuji; Prenen, Jean; Meseguer, Víctor; Owsianik, Grzegorz; Voets, Thomas; Nilius, Bernd

doi:10.1007/s00424-008-0493-6

Cited by 117 publications

(99 citation statements)

References 63 publications

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“…These two isoforms are expressed in the region containing the preBötC and an intracellular analogue of phosphatidylinositol 4,5 (PIP 2 ) leads to a FFA reversible augmentation of the inspiratory drive potential. This finding is consistent with the role of PIP 2 in regulating calcium-activated TRPM4 channels [89,90]. However, despite this circumstantial evidence, the molecular identity of the I CAN current remains unresolved.…”

Section: The Calcium-activated Nonselective Cationic Current In Cs Pasupporting

confidence: 84%

The role of spiking and bursting pacemakers in the neuronal control of breathing

et al. 2011

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Breathing is controlled by a distributed network involving areas in the neocortex, cerebellum, pons, medulla, spinal cord, and various other subcortical regions. However, only one area seems to be essential and sufficient for generating the respiratory rhythm: the preBötzinger complex (preBötC). Lesioning this area abolishes breathing and following isolation in a brain slice the preBötC continues to generate different forms of respiratory activities. The use of slice preparations led to a thorough understanding of the cellular mechanisms that underlie the generation of inspiratory activity within this network. Two types of inward currents, the persistent sodium current (I NaP ) and the calcium-activated nonspecific cation current (I CAN ), play important roles in respiratory rhythm generation. These currents give rise to autonomous pacemaker activity within respiratory neurons, leading to the generation of intrinsic spiking and bursting activity. These membrane properties amplify as well as activate synaptic mechanisms that are critical for the initiation and maintenance of inspiratory activity. In this review, we describe the dynamic interplay between synaptic and intrinsic membrane properties in the generation of the respiratory rhythm and we relate these mechanisms to rhythm generating networks involved in other behaviors.

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Section: The Calcium-activated Nonselective Cationic Current In Cs Pasupporting

confidence: 84%

The role of spiking and bursting pacemakers in the neuronal control of breathing

et al. 2011

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“…MO-induced TRPA1 currents were effectively inhibited by inclusion of neomycin in the pipette solution, due to a shielding effect of the negative charges of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) by neomycin (19). Therefore, we next examined effects of intracellularly applied neomycin on DPIinduced currents.…”

Section: Resultsmentioning

confidence: 99%

The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1 nociceptor

Suzuki

Hatano

Muraki

et al. 2014

American Journal of Physiology-Cell Physiology

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Transient receptor potential ankyrin 1 (TRPA1) is a Ca 2ϩ -permeable nonselective cation channel expressed in neuronal and nonneuronal cells and plays an important role in acute and inflammatory pain. Here, we show that an NADPH oxidase (NOX) inhibitor, diphenyleneiodonium (DPI), functions as a TRPA1 activator in human embryonic kidney cells expressing human TRPA1 (HEK-TRPA1) and in human fibroblast-like synoviocytes. Application of DPI at 0.03-10 M induced a Ca 2ϩ response in HEK-TRPA1 cells in a concentration-dependent manner. The Ca 2ϩ response was effectively blocked by a selective TRPA1 antagonist, HC-030031 (HC). In contrast, DPI had no effect on HEK cells expressing TRPV1-V4 or TRPM8. Four other NOX inhibitors, apocynin (APO), VAS2870 (VAS), plumbagin, and 2-acetylphenothiazine, also induced a Ca 2ϩ response in HEK-TRPA1 cells, which was inhibited by pretreatment with HC. In the presence of 5 mM glutathione, the Ca 2ϩ response to DPI was effectively reduced. Moreover, mutation of cysteine 621 in TRPA1 substantially inhibited the DPIinduced Ca 2ϩ response, while it did not inhibit the APO-and VASinduced responses. The channel activity was induced by DPI in excised membrane patches with both outside-out and inside-out configurations. Internal application of neomycin significantly inhibited the DPI-induced inward currents. In inflammatory synoviocytes with TRPA1, DPI evoked a Ca 2ϩ response that was sensitive to HC. In mice, intraplantar injection of DPI caused a pain-related response which was inhibited by preadministration with HC. Taken together, our findings demonstrate that DPI and other NOX inhibitors activate human TRPA1 without mediating NOX. calcium channel; transient receptor potential; NADPH oxidase inhibitors TRANSIENT RECEPTOR POTENTIAL ANKYRIN 1 (TRPA1), a Ca 2ϩ -permeable nonselective cation channel widely expressed in neuronal and nonneuronal cells, is activated by noxious cold, mechanical stimulation, irritant chemicals, and some clinical drugs (1,7,12,17,26,28,30,36). Because transgenic mice lacking TRPA1 have suppressed sensitivity to mechanical stimulation, cold stimuli, and TNF␣-induced mechanical hyperalgesia (5,8,20,23,33), the channel has been proposed to be a nociceptor mediating acute and inflammatory pain (3,23,33). Mutagenesis studies have revealed that the cysteine residues 414, 421, and 621 of human TRPA1 are targeted by physiological and nonphysiological electrophilic compounds that activate the channel (14, 26). In contrast, nonelectrophilic compounds, such as ⌬9-tetrahydrocannabinol, nicotine, and menthol, activate TRPA1 via unknown mechanisms (17,18,38). Because numerous structurally unrelated compounds stimulate TRPA1, greater attention should be given to whether common clinical drugs and experimental pharmacological agents activate the channel.The NADPH oxidases (NOXs), a family of transmembrane proteins comprising seven members (NOX1-NOX5, DUOX1, and DUOX2), function as transmembrane electron transporters that use cytosolic NADPH as electron donor and oxygen as electron a...

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“…Phosphatidylinositol 3 kinase inhibitors reduce TRPV1-mediated nociception (Zhuang et al, 2004). An indirect PIP 2 -mediated effect would explain the additional sensitization of the TRPA1 channels (Karashima et al, 2008;Kim et al, 2008b) as indicated by an enhanced early nociceptive response to Formalin in vivo and increased calcium influx in primary neurons of …”

Section: Discussionmentioning

confidence: 99%

Inhibitor κB Kinase β Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity

Bockhart¹,

Constantin²,

Häussler³

et al. 2009

J. Neurosci.

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Inhibitor B kinase (IKK) regulates the activity of the transcription factor nuclear factor-B that normally protects neurons against excitotoxicity. Constitutively active IKK is enriched at axon initial segments and nodes of Ranvier (NR). We used mice with a Cre-loxPmediated specific deletion of IKK␤ in sensory neurons of the dorsal root ganglion (SNS-IKK␤ Ϫ/Ϫ ) to evaluate whether IKK plays a role in sensory neuron excitability and nociception. We observed increased sensitivity to mechanical, cold, noxious heat and chemical stimulation in SNS-IKK␤ Ϫ/Ϫ mice, with normal proprioceptive and motor functions as revealed by gait analysis. This was associated with increased calcium influx and increased inward currents in small-and medium-sized primary sensory neurons of SNS-IKK␤ Ϫ/Ϫ mice during stimulation with capsaicin or Formalin, specific activators of transient receptor potentials TRPV1 and TRPA1 calcium channels, respectively. In vitro stimulation of saphenous nerve preparations of SNS-IKK␤ Ϫ/Ϫ mice showed increased neuronal excitability of A-and C-fibers but unchanged A-and C-fiber conduction velocities, normal voltage-gated sodium channel currents, and normal accumulation of ankyrin G and the sodium channels Nav1.6 at NR. The results suggest that IKK␤ functions as a negative modulator of sensory neuron excitability, mediated at least in part by modulation of TRP channel sensitivity.

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Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators

Cited by 117 publications

References 63 publications

The role of spiking and bursting pacemakers in the neuronal control of breathing

The role of spiking and bursting pacemakers in the neuronal control of breathing

The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1 nociceptor

Inhibitor κB Kinase β Deficiency in Primary Nociceptive Neurons Increases TRP Channel Sensitivity

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