Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons

Coste, Bertrand; Osorio, Nancy; Padilla, Françoise; Crest, Marcel; Delmas, Patrick

doi:10.1016/j.mcn.2004.01.015

Cited by 112 publications

(156 citation statements)

References 38 publications

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“…However, the presence of fluoride may affect some of the biophysical properties of the current. Intracellular fluoride has been reported to cause a hyperpolarizing shift in the voltage dependence of activation and inactivation of the persistent sodium current (30). The use of fluoride in our recordings allowed for unambiguous identification of neurons expressing the persistent sodium current; however, some properties may not be representative of the channel under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

Priest

Murphy

Lindia

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

249

220

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The transmission of pain signals after injury or inflammation depends in part on increased excitability of primary sensory neurons. Nociceptive neurons express multiple subtypes of voltagegated sodium channels (Na V1s), each of which possesses unique features that may influence primary afferent excitability. Here, we examined the contribution of Na V1.9 to nociceptive signaling by studying the electrophysiological and behavioral phenotypes of mice with a disruption of the SCN11A gene, which encodes Na V 1.9. Our results confirm that Na V1.9 underlies the persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion neurons but suggest that this current contributes little to mechanical thermal responsiveness in the absence of injury or to mechanical hypersensitivity after nerve injury or inflammation. However, the expression of Na V1.9 contributes to the persistent thermal hypersensitivity and spontaneous pain behavior after peripheral inflammation. These results suggest that inflammatory mediators modify the function of NaV1.9 to maintain inflammation-induced hyperalgesia.T he generation and propagation of action potentials in sensory neurons depends on the activity of voltage-gated sodium channels (Na V 1s). The differential expression of Na V 1 subtypes in distinct classes of sensory neurons, combined with their unique biophysical properties, suggest specific roles for each subtype in sensory transmission. Sodium channels in sensory neurons can be classified pharmacologically as sensitive to block by low nanomolar concentrations of tetrodotoxin (TTX) or resistant to Ͼ1 M TTX (1, 2).The contribution of TTX-resistant Na V 1 channel subtypes to the transmission of pain signals is an important area of focus: TTXresistant current carries the majority of charge during action potentials in nociceptive neurons (3), and this current is dynamically regulated in response to injury (4, 5). Na V 1.8, expressed primarily in C-fibers (6), underlies a TTX-resistant current with a high threshold for activation and steady-state inactivation and slow kinetics (7). Comparisons between dorsal root ganglion (DRG) neurons from WT and Na V 1.8 null mutant (Ϫ͞Ϫ) mice suggest that Na V 1.8 contributes the majority of the inward current flowing during action potentials in small-diameter neurons (8). Antisense oligonucleotides directed against Na V 1.8 implicate this channel in both neuropathic (9) and inflammatory (10) pain conditions in rats, although Na V 1.8Ϫ͞Ϫ mice displayed only a mild phenotype (7,11).The functional role of Na V 1.9, another subtype selectively expressed in nociceptors (12), remains poorly defined. The primary sequence of Na V 1.9 predicts that this subtype conducts sodium currents resistant to TTX (13). Indeed, a second TTX-resistant current is present in DRG neurons from Na V 1.8 knockout mice (14). This current has been referred to as the persistent, TTXresistant current because of its negative threshold for activation and depolarized midpoint of inactivation, resulting in a significant windo...

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Section: Discussionmentioning

confidence: 99%

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

Priest

Murphy

Lindia

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

249

220

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“…Young rats (male Wistar, 120 -130 g) were anesthetized with halothane and killed by severing of the carotid arteries in accordance with the Guide for the Care and Use of Laboratory Animals. Dissociation and cultures of DRG neurons were established from thoraco-lumbar DRGs as described previously (Coste et al, 2004;Coste et al, 2007;Maingret et al, 2008). Briefly, DRGs were freed from their connective tissue sheaths and incubated in enzyme solution containing 2 mg/ml collagenase IA (Sigma) for 45 min at 37°C and triturated in HBSS (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Multiple Desensitization Mechanisms of Mechanotransducer Channels Shape Firing of Mechanosensory Neurons

Hao¹,

Delmas²

2010

J. Neurosci.

112

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How desensitization of mechanotransducer currents regulates afferent signal generation in mammalian sensory neurons is essentially unknown. Here, we dissected desensitization mechanisms of mechanotransducer channels in rat sensory neurons that mediate the sense of touch and pain. We identified four types of mechanotransducer currents that distribute differentially in cutaneous nociceptors and mechanoreceptors and that differ in desensitization rates. Desensitization of mechanotransducer channels in mechanoreceptors was fast and mediated by channel inactivation and adaptation, which reduces the mechanical force sensed by the transduction channel. Both processes were promoted by negative voltage. These properties of mechanotransducer channels suited them to encode the dynamic parameters of the stimulus. In contrast, inactivation and adaptation of mechanotransducer channels in nociceptors had slow time courses and were suited to encode duration of the stimulus. Thus, desensitization properties of mechanotransducer currents relate to their functions as sensors of phasic and tonic stimuli and enable sensory neurons to achieve efficient stimulus representation.

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“…However, because fluoride causes a hyperpolarization shift in its voltage dependence (Coste et al, 2004), we preferred to use a chloride-based internal solution and a holding potential of Ϫ90 mV to remove resting inactivation. The activation threshold for Na v 1.9 (approximately Ϫ60 mV) is more negative than that of Na v 1.8 (ϳ30 mV) (Renganathan et al, 2002a;Coste et al, 2004), providing a window for observing Na v 1.9 currents in WT DRG neurons. Na ϩ currents were recorded from 60 WT DRG neurons in the presence of 300 nM TTX using a series of depolarizing voltage commands from Ϫ100 to 60 mV for 120 ms. Two distinct subpopulations were identified among the small neurons recorded.…”

Section: Sodium Currentsmentioning

confidence: 99%

The Voltage-Gated Sodium Channel Na_v1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity

Amaya¹,

Wang²,

Costigan³

et al. 2006

J. Neurosci.

273

231

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We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, ␣) gene that encodes the voltage-gated sodium channel Na v 1.9 to assess its contribution to pain. Na v 1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B 2 , and purinergic P2X 3 receptors. In Na v 1.9 ؊/؊ mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Na v 1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E 2 , bradykinin, interleukin-1␤, capsaicin, and P2X 3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na v 1.9 ؊/؊ mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na v 1.9 ؊/؊ mice. Na v 1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.

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Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons

Cited by 112 publications

References 38 publications

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

Multiple Desensitization Mechanisms of Mechanotransducer Channels Shape Firing of Mechanosensory Neurons

The Voltage-Gated Sodium Channel Na_v1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity

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Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons

Cited by 112 publications

References 38 publications

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na V 1.9 to sensory transmission and nociceptive behavior

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na V 1.9 to sensory transmission and nociceptive behavior

Multiple Desensitization Mechanisms of Mechanotransducer Channels Shape Firing of Mechanosensory Neurons

The Voltage-Gated Sodium Channel Nav1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity

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Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na _V 1.9 to sensory transmission and nociceptive behavior

The Voltage-Gated Sodium Channel Na_v1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity