Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action

Smith, Ewan St. John; Cadiou, Hervé; McNaughton, Peter A.

doi:10.1016/j.neuroscience.2006.12.024

Cited by 121 publications

(155 citation statements)

References 61 publications

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“…Rat pups were killed by cervical dislocation followed by decapitation. Culture methods were as described by Smith et al (2007). Briefly, individual DRG were removed and enzymatically isolated using collagenase.…”

Section: Dorsal Root Ganglion Neuronal Culturementioning

confidence: 99%

“…We used a modest pH excursion, to 6.3, for the majority of experiments in this study in view of the evidence that pH excursions are not large even in extreme inflammation and anoxia (Cobbe et al, 1982;Issberner et al, 1996). In most DRG neurons (95%), an inward current was evoked by application of a pH 6.3 solution (Smith et al, 2007). A non-inactivating current of small amplitude (Ϫ43.7 Ϯ 8.3 pA, n ϭ 6) ( Fig.…”

Section: Human Experimentsmentioning

confidence: 99%

“…Among the known interactions, peptides such as FMRFamide can enhance ASIC1 and 3 activity (Xie et al, 2003), and arachidonic acid can potentiate ASIC activation (Allen and Attwell, 2002;Smith et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Cadiou¹,

Studer²,

Jones³

et al. 2007

J. Neurosci.

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120

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Acid-sensing ion channels (ASICs) are a class of ion channels activated by extracellular protons and are believed to mediate the pain caused by tissue acidosis. Although ASICs have been widely studied, little is known about their regulation by inflammatory mediators. Here, we provide evidence that nitric oxide (NO) potentiates the activity of ASICs. Whole-cell patch-clamp recordings were performed on neonatal rat cultured dorsal root ganglion neurons and on ASIC isoforms expressed in CHO cells. The NO donor S-nitroso-Nacetylpenicillamine (SNAP) potentiates proton-gated currents in DRG neurons and proton-gated currents in CHO cells expressing each of the acid-sensitive ASIC subunits. Modulators of the cGMP/PKG pathway had no effect on the potentiation, but in excised patches from CHO cells expressing ASIC2a, the potentiation could be reversed by externally applied reducing agents. NO therefore has a direct external effect on the ASIC ion channel, probably through oxidization of cysteine residues. Complementary psychophysiological studies were performed using iontophoresis of acidic solutions through the skin of human volunteers. Topical application of the NO donor glyceryl trinitrate significantly increased acid-evoked pain but did not affect heat or mechanical pain thresholds. ASICs may therefore play an important role in the pain associated with metabolic stress and inflammation, where both tissue acidosis and a high level of NO are present.

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Section: Dorsal Root Ganglion Neuronal Culturementioning

confidence: 99%

Section: Human Experimentsmentioning

confidence: 99%

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Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Cadiou¹,

Studer²,

Jones³

et al. 2007

J. Neurosci.

Self Cite

120

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“…Sensory neurones express several acid sensors: acid‐sensing ion channels (ASICs), transient receptor potential vanilloid 1 (TRPV1), proton‐sensing GPCRs and certain background K + channels 18. Furthermore, response to low pH has been shown to be sensitized by inflammatory mediators 19, 20, 21, 22, 23, 24…”

Section: Introductionmentioning

confidence: 99%

Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate

Wright

Husson

et al. 2018

NMR in Biomedicine

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Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1‐13C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate‐to‐pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the 13CO2/H13CO3 − ratio, in animals injected with hyperpolarized H13CO3 −, to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA‐induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid‐sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA‐induced inflammation.

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“…The activatory properties of arachidonic acid and its direct action have been confirmed by a recent study on native ASIC channels in rat primary sensory neurons. 58 However, our finding that both the activatory and inhibitory effects of amitriptyline are stronger at pH 7.4 compared to pH 8.4 (where the deprotonated lipid-soluble form of the drug is increased ten-fold) favors a direct interaction with the extracellular domain of the channel. Nevertheless, we cannot rule out at the present stage an indirect mechanism, since inhibition of M current by 10 μM imipramine in rat sympathetic neurons by PLC activation followed by PIP 2 depletion has been recently proved.…”

Section: Resultsmentioning

confidence: 71%

ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases

Marin¹,

Prica²,

Amuzescu³

et al. 2008

Channels

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Analgesia induced by certain tricyclic antidepressants has been largely used for decades, yet the mechanisms involved are incompletely understood. Starting from previously reported dual effects of amitriptyline on wild-type ENaC (see ref. 39), we extended our study to ASIC1a by performing a series of whole cell and singlechannel recordings of proton-activated currents in HEK293 cells. Acid pulses were applied at 2 or 5 min intervals, and amitriptyline (1-500 μM) was applied at a holding pH of 7.4 or 8.4 between pulses. Dose-response plots were fitted with dual Hill type functions, yielding a half-activatory constant of 0.3 μM and a half-inhibitory constant of 382 μM at pH 7.4. At pH 8.4 both constants were shifted to higher values (0.5 and 444 μM, respectively). In whole-cell experiments, FMRF-amide increased the peak amplitude of ASIC1a transients at 0.1 μM and decreased it at 1 and 100 μM. Single-channel recordings were idealized and fitted using an 8-state linear connectivity model comprising four consecutive activation steps. Both amitriptyline (1 μM) and FMRF-amide (0.1 μM) increased the unitary current amplitude, and modified the opening and closing rates of the first gating mode. They also increased the transition rate from the second to the first gating mode, and the rate of final closure. The activatory effect of both compounds vanished after a mild trypsin pretreatment, suggesting the existence of activatory sites for FMRF-amide and amitriptyline in the outer vestibule of ASIC1a, which can be removed by exo-or endogenous serine-proteases.

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Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action

Cited by 121 publications

References 61 publications

Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate

ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases

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Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action

Cited by 121 publications

References 61 publications

Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Modulation of Acid-Sensing Ion Channel Activity by Nitric Oxide

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

ASIC1a activation by amitriptyline and FMRF-amide is removed by serine proteases

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Increased hyperpolarized [1‐¹³C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized ¹³C‐labelled bicarbonate