Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca<sup>2+</sup> response elicited by repeated application of capsaicin in rat DRG neurons

Zhang, Xiulin; Daugherty, Stephanie L.; Groat, William C. de

doi:10.1152/ajpregu.00672.2010

Cited by 31 publications

(44 citation statements)

References 53 publications

(85 reference statements)

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“…In agreement with other reports (Ruparel et al, 2008), we observed homologous desensitization of the capsaicin response in 90% of the neurons (164/182, 4 rats) (Fig.2C) and desensitization of the AITC response in 60% of the neurons (105/174, 4 rats) (Fig.2B). A potentiation (i.e., a second response that was larger than first one) was detected in 10% of capsaicin responsive neurons as described previously (Zhang et al, 2011) and in 40% of AITC responsive neurons. Homologous desensitization of OA-NO 2 was detected in 90% of neurons (177/197, 4 rats) (Fig.2A); and potentiation occurred in the remaining 10% of neurons.…”

Section: Resultssupporting

confidence: 74%

“…After a laminectomy under isoflurane anesthesia L4 - L6 DRGs were removed bilaterally, enzymatically treated (collagenase type 4, 2mg/ml and trypsin, 1mg/ml; Worthington Biochemical, Lakewood, NJ) and mechanically dissociated as described elsewhere (Zhang et al, 2011). The cells were plated on poly-l-lysine-coated glass coverslips (Sigma, St. Louis, MO) and incubated at 37°C in 5% CO 2 and 90% humidity for at least 3-4 h before Ca 2+ imaging or patch clamp recording.…”

Section: Methodsmentioning

confidence: 99%

“…Fura 2-AM was dissolved in Hank's balanced salt solution (HBSS) containing (in mM): 138 NaCl, 5 KCl, 0.3 KH 2 PO 4 , 4 NaHCO 3 , 2 CaCl 2 , 1 MgCl 2 , 10 HEPES, and 5.6 glucose, pH 7.4. Ca 2+ imaging was performed as previously (Zhang et al, 2011). Briefly, coverslips were placed on an epifluorescence microscope (Olympus IX70) and continuously perfused (2–3 ml/min) with HBSS.…”

Section: Methodsmentioning

confidence: 99%

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Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Zhang

Koronowski

et al. 2014

Experimental Neurology

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Nitro-oleic acid (OA-NO2), an electrophilic fatty acid nitroalkene byproduct of redox reactions, activates transient receptor potential ion channels (TRPA1 and TRPV1) in primary sensory neurons. To test the possibility that signaling actions of OA-NO2 might modulate TRP channels, we examined: (1) interactions between OA-NO2 and other agonists for TRPA1 (allyl-isothiocyanate, AITC) and TRPV1 (capsaicin) in rat dissociated dorsal root ganglion cells using Ca2+ imaging and patch clamp techniques and (2) interactions between these agents on sensory nerves in the rat hindpaw. Ca2+ imaging revealed that brief application (15-30 sec) of each of the three agonists induced homologous desensitization. Heterologous desensitization also occurred when one agonist was applied prior to another agonist. OA-NO2 was more effective in desensitizing the response to AITC than the response to capsaicin. Prolonged exposure to OA-NO2 (20 min) had a similar desensitizing effect on AITC or capsaicin. Homologous and heterologous desensitization were also demonstrated with patch clamp recording. Deltamethrin, a phosphatase inhibitor, reduced the capsaicin or AITC induced desensitization of OA-NO2 but did not suppress the OA-NO2 induced desensitization of AITC or capsaicin, indicating that heterologous desensitization induced by either capsaicin or AITC occurs by a different mechanism than the desensitization produced by OA-NO2. Subcutaneous injection of OA-NO2 (2.5 mM, 35 μL) into a rat hindpaw induced delayed and prolonged nociceptive behavior. Homologous desensitization occurred with AITC and capsaicin when applied at 15 minute intervals, but did not occur with OA-NO2 when applied at a 30 min interval. Pretreatment with OA-NO2 reduced AITC-evoked nociceptive behaviors but did not alter capsaicin responses. These results raise the possibility that OA-NO2 might be useful clinically to reduce neurogenic inflammation and certain types of painful sensations by desensitizing TRPA1 expressing nociceptive afferents.

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Section: Resultssupporting

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Zhang

Koronowski

et al. 2014

Experimental Neurology

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“…Inclusion of CaMKII/calmodulin in the pipette in whole cell recordings promoted recovery from desensitisation (Jung et al 2004). Although TRPV1 activation leads to desensitisation, some stimulation protocols can potentiate TRPV1 activity, and this potentiation can be inhibited by CaMKII and MEK inhibitors but not inhibitors of PKC or PKA signalling (Firner et al 2006;Zhang et al 2011). In addition, MAPK inhibitors have been reported to reduce NGF sensitisation of TRPV1 (Bonnington and McNaughton 2003;Zhu and Oxford 2007;Zhuang et al 2004).…”

Section: Phosphorylationmentioning

confidence: 99%

Trpv1

Bevan¹,

Quallo²,

Andersson³

2014

Handbook of Experimental Pharmacology

141

124

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TRPV1 is a well-characterised channel expressed by a subset of peripheral sensory neurons involved in pain sensation and also at a number of other neuronal and non-neuronal sites in the mammalian body. Functionally, TRPV1 acts as a sensor for noxious heat (greater than ~42 °C). It can also be activated by some endogenous lipid-derived molecules, acidic solutions (pH < 6.5) and some pungent chemicals and food ingredients such as capsaicin, as well as by toxins such as resiniferatoxin and vanillotoxins. Structurally, TRPV1 subunits have six transmembrane (TM) domains with intracellular N- (containing 6 ankyrin-like repeats) and C-termini and a pore region between TM5 and TM6 containing sites that are important for channel activation and ion selectivity. The N- and C- termini have residues and regions that are sites for phosphorylation/dephosphorylation and PI(4,5)P2 binding, which regulate TRPV1 sensitivity and membrane insertion. The channel has several interacting proteins, some of which (e.g. AKAP79/150) are important for TRPV1 phosphorylation. Four TRPV1 subunits form a non-selective, outwardly rectifying ion channel permeable to monovalent and divalent cations with a single-channel conductance of 50-100 pS. TRPV1 channel kinetics reveal multiple open and closed states, and several models for channel activation by voltage, ligand binding and temperature have been proposed. Studies with TRPV1 agonists and antagonists and Trpv1 (-/-) mice have suggested a role for TRPV1 in pain, thermoregulation and osmoregulation, as well as in cough and overactive bladder. TRPV1 antagonists have advanced to clinical trials where findings of drug-induced hyperthermia and loss of heat sensitivity have raised questions about the viability of this therapeutic approach.

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“…Application of QX-314 together with capsaicin produced long-lasting inhibition of voltagedependent sodium channels in TRPV1-expressing neurons and selectively blocked function of specific populations of sensory neurons in vivo Kim et al 2010), suggestive of QX-314 entry through TRPV1 channels followed by block of sodium channels. However, another possibility is that QX-314 does not permeate directly through TRPV1 channels but instead enters cells through some pathway activated secondarily by TRPV1 stimulation, which produces many downstream signaling events (e.g., Mohapatra and Nau 2005; Wu et al 2005;Zhang et al 2011). In the case of P2X7 purinergic receptors, originally proposed to form pores capable of passing molecules as large as YO-PRO (Virginio et al 1999), it was later suggested that such molecules may instead enter through large-pore pannexin channels activated indirectly by P2X7 stimulation (Pelegrin et al 2006;cf.…”

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Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

Puopolo

Binshtok

Yao

et al. 2013

Journal of Neurophysiology

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Puopolo M, Binshtok AM, Yao GL, Oh SB, Woolf CJ, Bean BP. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. J Neurophysiol 109: 1704 -1712, 2013. First published January 9, 2013 doi:10.1152 doi:10. /jn.00012.2013) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of "pore dilation" previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with P QX-314 /P Cs ϭ 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50 -100 M. We conclude that QX-314 is directly permeant in the "standard" pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry.

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Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca²⁺ response elicited by repeated application of capsaicin in rat DRG neurons

Cited by 31 publications

References 53 publications

Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Trpv1

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

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Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca2+ response elicited by repeated application of capsaicin in rat DRG neurons

Cited by 31 publications

References 53 publications

Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Nitro-oleic acid desensitizes TRPA1 and TRPV1 agonist responses in adult rat DRG neurons

Trpv1

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

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Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca²⁺ response elicited by repeated application of capsaicin in rat DRG neurons