Jacques Noel - Academia.edu (original) (raw)
Papers by Jacques Noel
Diet induced obesity is one of the major causes of obesity, which affects 13% of the world's ... more Diet induced obesity is one of the major causes of obesity, which affects 13% of the world's adult population. Obesity is correlated to chronic pain regardless of other components of the metabolic syndrome. Our study focuses on investigating the effect of high-fat diet induced obesity on peripheral sensory neurons activity and pain perception, followed by deciphering the underlying cellular and molecular mechanisms that involve Acid-Sensing Ion Channel 3 (ASIC3). We show here that heat sensitive C-fibers from mice made obese by consumption of a high-fat diet exhibited an increased activity during baseline and upon heating. Obese mice showed long-lasting heat pain hypersensitivity once obesity was well established, while mechanical sensitivity was not affected. We found that the serum of obese mice was enriched in lysophosphatidylcholine (LPC) species (LPC16:0, LPC18:0 and LPC18:1), which activate ASIC3 channels and increased peripheral neuron excitability. Genetic deletion and i...
Cahiers Orstom Serie Oceanographie, 1969
Biochemical Society Transactions, Jun 1, 1999
A,B, Effects of 4-AP (3 mM, A) and TEA (10 mM, B) on I(V) relationships of total MS currents reco... more A,B, Effects of 4-AP (3 mM, A) and TEA (10 mM, B) on I(V) relationships of total MS currents recorded using KCl-based pipette solutions.
Journal of Biological Chemistry, 1991
TRESK (K2P18.1) is a background K+ channel highly expressed in dorsal root and trigeminal ganglia... more TRESK (K2P18.1) is a background K+ channel highly expressed in dorsal root and trigeminal ganglia sensory neurons, where it has been involved in modulating sensory neuron excitability and firing. Reduction in channel expression and function has been reported to enhance nociceptors excitability after injury or inflammation, but its role in somatosensory perception and nociception is still poorly understood. Here we show that TRESK regulates the sensitivity to mechanical and cold stimuli, but it is not involved in the perception of heat. Small/medium-sized DRG sensory neurons from TRESK knockout mice (KO) present an enhanced excitability and recordings from skin nociceptive C-fibers show an increased activation at lower intensity stimulus in response to cold and mechanical stimulation in the absence of the channel. In agreement, mice lacking TRESK present mechanical and cold hypersensitivity compared to wild-type littermates, while heat sensitivity is unaltered. TRESK is also involved...
The Journal of Neuroscience, 2000
AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have develop... more AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have developed antibodies that recognize all AMPA or all NMDA receptor variants on the surface of living neurons. AMPA receptor variants were identified with a polyclonal antibody recognizing the conserved extracellular loop region of all four AMPA receptor subunits (GluR1–4, bothflipandflop), whereas NMDA receptors were immunolabeled with a polyclonal antibody that binds to an extracellular N-terminal epitope of the NR1 subunit, common to all splice variants. In non-fixed brain sections these antibodies gave labeling patterns similar to autoradiographic distributions with particularly high levels in the hippocampus. Using these antibodies, in conjunction with GluR2-specific and synaptophysin antibodies, we have directly localized and quantified surface-expressed native AMPA and NMDA receptors on cultured living hippocampal neurons during development. Using a quantitative cell ELISA, a dramatic incr...
The Journal of Neuroscience, 2016
Cold temperature detection involves the process of sensory transduction in cutaneous primary sens... more Cold temperature detection involves the process of sensory transduction in cutaneous primary sensory nerve terminals, which converts thermal stimuli into depolarizations of the membrane. This transformation into electrical signals is followed by the subsequent propagation of action potentials in cold-sensitive afferent nerve fibers. A large array of ion channels shapes this process; however, the precise contribution of specific ion channel subtypes to cold perception and cold pain remains elusive. This review aims at giving an update on our current understanding of the role played by TRPs, leak K+and voltage-gated Na+and K+channels in the transduction of cold by nociceptors and in cold-induced pain.
Biochemical Journal, 1992
In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production ... more In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production of Ins(1,4,5)P3 through the degradation of membrane polyphosphoinositides [PtdIns(4,5)P2]. InsP3 evokes in turn the release of Ca2+ from internal stores. Our results show that the internal perfusion of single guinea-pig hepatocytes with monoclonal anti-PtdInsP2 antibody blocks the rise in cytosolic free Ca2+ concn. ([Ca2+]i) evoked by noradrenaline, an InsP3-dependent agonist, but not by the monohydroxylated bile acid taurolithocholate 3-sulphate, which is known to permeabilize the endoplasmic reticulum. In these conditions, the bile acid elicited either fast or slow fluctuations of [Ca2+]i independently of any InsP3 production. The responses to the bile acid were also observed in the absence of external Ca2+. The presence of intracellular anti-PtdInsP2 antibody does not affect the response to a photolytic release of InsP3 (1.5 microM final concn.) from a caged precursor.
![Research paper thumbnail of Cyclic AMP-evoked oscillations of intracellular [Ca2+] in guinea-pig hepatocytes](https://attachments.academia-assets.com/102475574/thumbnails/1.jpg)
](Biochemical Journal, 1991
The effects of the beta-adrenoceptor agonist isoprenaline and cyclic AMP (cAMP) on cytosolic free... more The effects of the beta-adrenoceptor agonist isoprenaline and cyclic AMP (cAMP) on cytosolic free Ca2+ ([Ca2+]i) were studied in the single guinea-pig hepatocyte. In common with InsP3-dependent agonists such as noradrenaline or angiotensin II, isoprenaline (0.5-10 microM) and cAMP (50-100 mM, perfused into the cell via the patch-pipette), were able to generate fast and slow fluctuations of [Ca2+]i. Responses to isoprenaline and cAMP also were observed in the absence of external Ca2+. Isoprenaline-evoked [Ca2+]i rises were not blocked by the intracellular perfusion of heparin, suggesting that these fluctuations are independent of the binding of InsP3 to its receptor.
Nature Neuroscience, 2000
Cell reports, Jan 19, 2015
Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. Howev... more Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological co...
Cell reports, Jan 14, 2015
The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expres... more The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), Aδ- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fund...
The Journal of Neuroscience, 2011
Iatrogenic pain consecutive to a large number of surgical procedures has become a growing health ... more Iatrogenic pain consecutive to a large number of surgical procedures has become a growing health concern. The etiology and pathophysiology of postoperative pain are still poorly understood, but hydrogen ions appear to be important in this process. We have investigated the role of peripheral acid-sensing ion channels (ASICs), which form depolarizing channels activated by extracellular protons, in a rat model of postoperative pain (i.e., hindpaw skin/muscle incision). We report high levels of ASIC-type currents (∼77%) in sensory neurons innervating the hindpaw muscles, with a prevalence of ASIC3-like currents. The ASIC3 protein is largely expressed in lumbar DRG neurons innervating the plantar muscle, and its mRNA and protein levels are increased by plantar incision 24 h after surgery. Pharmacological inhibition of ASIC3 channels with the specific toxin APETx2 orin vivoknockdown of ASIC3 subunit by small interfering RNA led to a significant reduction of postoperative spontaneous, ther...
Proceedings of the National Academy of Sciences, 2012
In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particula... more In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particularly important sensor of nonadaptive pain associated with tissue acidosis. However, little is known about the human ASIC3 channel, which includes three splice variants differing in their C-terminal domain (hASIC3a, hASIC3b, and hASIC3c). hASIC3a transcripts represent the main mRNAs expressed in both peripheral and central neuronal tissues (dorsal root ganglia [DRG], spinal cord, and brain), where a small proportion of hASIC3c transcripts is also detected. We show that hASIC3 channels (hASIC3a, hASIC3b, or hASIC3c) are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0), an original and inducible property yet unknown. When the external pH decreases, hASIC3 display a transient acid mode with brief activation that is relevant to the classical ASIC currents, as previously described. On the other hand, an ext...
Diet induced obesity is one of the major causes of obesity, which affects 13% of the world's ... more Diet induced obesity is one of the major causes of obesity, which affects 13% of the world's adult population. Obesity is correlated to chronic pain regardless of other components of the metabolic syndrome. Our study focuses on investigating the effect of high-fat diet induced obesity on peripheral sensory neurons activity and pain perception, followed by deciphering the underlying cellular and molecular mechanisms that involve Acid-Sensing Ion Channel 3 (ASIC3). We show here that heat sensitive C-fibers from mice made obese by consumption of a high-fat diet exhibited an increased activity during baseline and upon heating. Obese mice showed long-lasting heat pain hypersensitivity once obesity was well established, while mechanical sensitivity was not affected. We found that the serum of obese mice was enriched in lysophosphatidylcholine (LPC) species (LPC16:0, LPC18:0 and LPC18:1), which activate ASIC3 channels and increased peripheral neuron excitability. Genetic deletion and i...
Cahiers Orstom Serie Oceanographie, 1969
Biochemical Society Transactions, Jun 1, 1999
A,B, Effects of 4-AP (3 mM, A) and TEA (10 mM, B) on I(V) relationships of total MS currents reco... more A,B, Effects of 4-AP (3 mM, A) and TEA (10 mM, B) on I(V) relationships of total MS currents recorded using KCl-based pipette solutions.
Journal of Biological Chemistry, 1991
TRESK (K2P18.1) is a background K+ channel highly expressed in dorsal root and trigeminal ganglia... more TRESK (K2P18.1) is a background K+ channel highly expressed in dorsal root and trigeminal ganglia sensory neurons, where it has been involved in modulating sensory neuron excitability and firing. Reduction in channel expression and function has been reported to enhance nociceptors excitability after injury or inflammation, but its role in somatosensory perception and nociception is still poorly understood. Here we show that TRESK regulates the sensitivity to mechanical and cold stimuli, but it is not involved in the perception of heat. Small/medium-sized DRG sensory neurons from TRESK knockout mice (KO) present an enhanced excitability and recordings from skin nociceptive C-fibers show an increased activation at lower intensity stimulus in response to cold and mechanical stimulation in the absence of the channel. In agreement, mice lacking TRESK present mechanical and cold hypersensitivity compared to wild-type littermates, while heat sensitivity is unaltered. TRESK is also involved...
The Journal of Neuroscience, 2000
AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have develop... more AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have developed antibodies that recognize all AMPA or all NMDA receptor variants on the surface of living neurons. AMPA receptor variants were identified with a polyclonal antibody recognizing the conserved extracellular loop region of all four AMPA receptor subunits (GluR1–4, bothflipandflop), whereas NMDA receptors were immunolabeled with a polyclonal antibody that binds to an extracellular N-terminal epitope of the NR1 subunit, common to all splice variants. In non-fixed brain sections these antibodies gave labeling patterns similar to autoradiographic distributions with particularly high levels in the hippocampus. Using these antibodies, in conjunction with GluR2-specific and synaptophysin antibodies, we have directly localized and quantified surface-expressed native AMPA and NMDA receptors on cultured living hippocampal neurons during development. Using a quantitative cell ELISA, a dramatic incr...
The Journal of Neuroscience, 2016
Cold temperature detection involves the process of sensory transduction in cutaneous primary sens... more Cold temperature detection involves the process of sensory transduction in cutaneous primary sensory nerve terminals, which converts thermal stimuli into depolarizations of the membrane. This transformation into electrical signals is followed by the subsequent propagation of action potentials in cold-sensitive afferent nerve fibers. A large array of ion channels shapes this process; however, the precise contribution of specific ion channel subtypes to cold perception and cold pain remains elusive. This review aims at giving an update on our current understanding of the role played by TRPs, leak K+and voltage-gated Na+and K+channels in the transduction of cold by nociceptors and in cold-induced pain.
Biochemical Journal, 1992
In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production ... more In liver cells, the stimulation of alpha 1-adrenoceptors by noradrenaline induces the production of Ins(1,4,5)P3 through the degradation of membrane polyphosphoinositides [PtdIns(4,5)P2]. InsP3 evokes in turn the release of Ca2+ from internal stores. Our results show that the internal perfusion of single guinea-pig hepatocytes with monoclonal anti-PtdInsP2 antibody blocks the rise in cytosolic free Ca2+ concn. ([Ca2+]i) evoked by noradrenaline, an InsP3-dependent agonist, but not by the monohydroxylated bile acid taurolithocholate 3-sulphate, which is known to permeabilize the endoplasmic reticulum. In these conditions, the bile acid elicited either fast or slow fluctuations of [Ca2+]i independently of any InsP3 production. The responses to the bile acid were also observed in the absence of external Ca2+. The presence of intracellular anti-PtdInsP2 antibody does not affect the response to a photolytic release of InsP3 (1.5 microM final concn.) from a caged precursor.
Biochemical Journal, 1991
The effects of the beta-adrenoceptor agonist isoprenaline and cyclic AMP (cAMP) on cytosolic free... more The effects of the beta-adrenoceptor agonist isoprenaline and cyclic AMP (cAMP) on cytosolic free Ca2+ ([Ca2+]i) were studied in the single guinea-pig hepatocyte. In common with InsP3-dependent agonists such as noradrenaline or angiotensin II, isoprenaline (0.5-10 microM) and cAMP (50-100 mM, perfused into the cell via the patch-pipette), were able to generate fast and slow fluctuations of [Ca2+]i. Responses to isoprenaline and cAMP also were observed in the absence of external Ca2+. Isoprenaline-evoked [Ca2+]i rises were not blocked by the intracellular perfusion of heparin, suggesting that these fluctuations are independent of the binding of InsP3 to its receptor.
Nature Neuroscience, 2000
Cell reports, Jan 19, 2015
Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. Howev... more Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological co...
Cell reports, Jan 14, 2015
The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expres... more The T-type calcium channel Cav3.2 emerges as a key regulator of sensory functions, but its expression pattern within primary afferent neurons and its contribution to modality-specific signaling remain obscure. Here, we elucidate this issue using a unique knockin/flox mouse strain wherein Cav3.2 is replaced by a functional Cav3.2-surface-ecliptic GFP fusion. We demonstrate that Cav3.2 is a selective marker of two major low-threshold mechanoreceptors (LTMRs), Aδ- and C-LTMRs, innervating the most abundant skin hair follicles. The presence of Cav3.2 along LTMR-fiber trajectories is consistent with critical roles at multiple sites, setting their strong excitability. Strikingly, the C-LTMR-specific knockout uncovers that Cav3.2 regulates light-touch perception and noxious mechanical cold and chemical sensations and is essential to build up that debilitates allodynic symptoms of neuropathic pain, a mechanism thought to be entirely A-LTMR specific. Collectively, our findings support a fund...
The Journal of Neuroscience, 2011
Iatrogenic pain consecutive to a large number of surgical procedures has become a growing health ... more Iatrogenic pain consecutive to a large number of surgical procedures has become a growing health concern. The etiology and pathophysiology of postoperative pain are still poorly understood, but hydrogen ions appear to be important in this process. We have investigated the role of peripheral acid-sensing ion channels (ASICs), which form depolarizing channels activated by extracellular protons, in a rat model of postoperative pain (i.e., hindpaw skin/muscle incision). We report high levels of ASIC-type currents (∼77%) in sensory neurons innervating the hindpaw muscles, with a prevalence of ASIC3-like currents. The ASIC3 protein is largely expressed in lumbar DRG neurons innervating the plantar muscle, and its mRNA and protein levels are increased by plantar incision 24 h after surgery. Pharmacological inhibition of ASIC3 channels with the specific toxin APETx2 orin vivoknockdown of ASIC3 subunit by small interfering RNA led to a significant reduction of postoperative spontaneous, ther...
Proceedings of the National Academy of Sciences, 2012
In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particula... more In rodent sensory neurons, acid-sensing ion channel 3 (ASIC3) has recently emerged as a particularly important sensor of nonadaptive pain associated with tissue acidosis. However, little is known about the human ASIC3 channel, which includes three splice variants differing in their C-terminal domain (hASIC3a, hASIC3b, and hASIC3c). hASIC3a transcripts represent the main mRNAs expressed in both peripheral and central neuronal tissues (dorsal root ganglia [DRG], spinal cord, and brain), where a small proportion of hASIC3c transcripts is also detected. We show that hASIC3 channels (hASIC3a, hASIC3b, or hASIC3c) are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0), an original and inducible property yet unknown. When the external pH decreases, hASIC3 display a transient acid mode with brief activation that is relevant to the classical ASIC currents, as previously described. On the other hand, an ext...