Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons

Fjell, Jenny; Cummins, Theodore R.; Dib‐Hajj, Sulayman D.; Fried, Kaj; Black, Joel A.; Waxman, Stephen G.

doi:10.1016/s0169-328x(99)00070-4

Cited by 192 publications

(139 citation statements)

References 69 publications

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“…4D; Table 2; p Ͻ 0.001, Student's t test). Thus, the properties of TTX-R I Na recorded from EGFP-positive DRG neurons were similar to TTX-R I Na recorded previously from DRG neurons and heterologously expressed Na v 1.8 channels in sympathetic neurons (Akopian et al, 1999;Fjell et al, 1999aFjell et al, , 1999bSchofield et al, 2008;Han et al, 2014). Overall, EGFP expression in Scn10a-EGFP mice correlates well with the presence of Na v 1.8.…”

Section: Egfp Expression In Drg Neurons and Primary Sensory Afferentssupporting

confidence: 80%

A 3.7 kb Fragment of the MouseScn10aGene Promoter Directs Neural Crest But Not Placodal Lineage EGFP Expression in a Transgenic Animal

Ikeda

Puhl

2015

J. Neurosci.

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Under physiological conditions, the voltage-gated sodium channel Na v 1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Na v 1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Na v 1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFPpositive (mean diameter ϭ 26.5 m). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (ϳ10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Na v 1.8 transcript (95%), Na v 1.8-immunoreactivity (70%), and TTX-R I Na (100%), although not all Na v 1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Na v 1.8-immunoreactivity confirmed Na v 1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R I Na recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Na v 1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Na v 1.8 expression pattern in neural crest-derived sensory neurons.

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Section: Egfp Expression In Drg Neurons and Primary Sensory Afferentssupporting

confidence: 80%

A 3.7 kb Fragment of the MouseScn10aGene Promoter Directs Neural Crest But Not Placodal Lineage EGFP Expression in a Transgenic Animal

Ikeda

Puhl

2015

J. Neurosci.

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“…The expression of rNa v 1.9a is dynamic and is modulated by the action of neurotrophic factors. Rat Na v 1.9a transcripts and protein and the current attributable to rNa v 1.9a are significantly down-regulated in vivo after axotomy or chronic constriction injury of the sciatic nerve (14,17,47) and in an in vitro model of axotomy (47,48). Expression of rNa v 1.9a after axotomy is restored by exposure to the neurotrophic factor glial derived neurotrophic factor, but not nerve growth factor (47,48).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)

Liu

Dib‐Hajj

Waxman

2001

Journal of Biological Chemistry

119

124

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In this study we demonstrate a direct interaction between a cytosolic fibroblast growth factor family member and a sodium channel. A yeast two-hybrid screen for proteins that associate with the cytoplasmic domains of the tetrodotoxin-resistant sodium channel rNa v 1.9a (NaN) led to the identification of fibroblast growth factor homologous factor 1B (FHF1B), a member of the fibroblast growth factor family, as an interacting partner of rNa v 1.9a. FHF1B selectively interacts with the C-terminal region but not the other four intracellular segments of rNa v 1.9a. FHF1B binds directly to the Cterminal polypeptide of rNa v 1.9a both in vitro and in mammalian cell lines. The N-terminal 5-77 amino acid residues of FHF1B are essential for binding to rNa v 1.9a. FHF1B did not interact with C termini of two other sodium channels hNa v 1.7a (hNaNE) and rNa v 1.8a (SNS), which share 50% similarity to the C-terminal polypeptide of rNa v 1.9a. FHF1B is the first growth factor found to bind specifically to a sodium channel. Although the functional significance of this interaction is not clear, FHF1B may affect the rNa v 1.9a channel directly or by recruiting other proteins to the channel complex. Alternatively, it is possible that rNa v 1.9a may help deliver this factor to the cell membrane, where it exerts its function.

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“…Evidence is accumulating that NGF may exert such effects by causing changes in ionic currents (such as Na ϩ and K ϩ currents) responsible for AP electrogenesis in DRG neurons (Oyelese et al, 1997;Fjell et al, 1999a;Everill and Kocsis, 2000). Together these findings suggest that the inflammation-induced changes in the somatic AP configuration in nociceptive neurons may result from actions of NGF.…”

Section: Abstract: Nociceptive Neurons; Drg; Hyperalgesia; Ngf; Firimentioning

confidence: 96%

“…They may result from the known regulatory effects of NGF on expression of a variety of ion channel types in DRG neurons, although other neurotrophins such as GDNF may contribute to this regulation (Fjell et al, 1999a). NGF dependence has been established for certain Na ϩ (see above) and K ϩ (the transient I A and the sustained I K ) channel and currents (Everill and Kocsis, 2000), but has not been studied for some of the channel types (such as those responsible for I h, I KC a, IK (IR) ) that could contribute to altered firing frequency or spontaneous activity seen here.…”

Section: Ngf Dependencementioning

confidence: 99%

Time Course and Nerve Growth Factor Dependence of Inflammation-Induced Alterations in Electrophysiological Membrane Properties in Nociceptive Primary Afferent Neurons

et al. 2001

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Novel findings of changes in nociceptive dorsal root ganglion (DRG) neurons during hindlimb inflammation induced by complete Freund's adjuvant (CFA) injections in the hindpaw and hindleg are reported. These include increased maximum fiber following frequency in nociceptive C-and A␦-fiber units by 2.7 and 3 times, respectively, and increased incidence of ongoing (spontaneous) activity by 3.3 times (to 54%) and 2.4 times (to 27%), respectively. These changes and the CFA-induced changes in somatic action potential (AP) configuration in nociceptive neurons were incomplete 24 hr after CFA. The nerve growth factor (NGF) dependence of the inflammation-induced changes was examined by injecting a synthetic NGF sequestering protein [tyrosine receptor kinase A Ig2 (trkA Ig2)] with CFA and subsequently into the CFA injection sites. NGF sequestration prevented some CFA-induced changes in nociceptive neurons including: the increased fiber following frequency (C and A␦), the increased proportions of units with ongoing activity (C and A␦), the decreased AP duration (C and A␦), but not the decreased afterhyperpolarization (AHP) durations (C, A␦, and A␣/␤) . AP variables of nociceptive units with spontaneous activity were examined.The time course of electrophysiological changes in nociceptive units is consistent with processes involving altered protein expression and/or retrograde transport of factors. These results (1) implicate NGF in regulating inflammation-induced decreases in AP duration and in increases in firing rate and spontaneous activity but not in decreases in AHP duration and (2) suggest clinical advantages of reducing NGF in some inflammatory pain states. Key words: nociceptive neurons; DRG; hyperalgesia; NGF; firing rate; spontaneous activityInflammation is accompanied by hyperalgesia and allodynia. The underlying neuronal mechanisms are not fully understood, but short-term (hours) changes at more than one level of the nociceptive pathway occur, including sensitization of peripheral terminals and of central pathways (for review, see Millan, 1999). However, it is clear that longer term (days) changes in the electrical properties of the entire primary afferent neuron also occur during inflammation. These include decreased durations both of somatic action potentials (APs) in nociceptive C-and A␦-fiber units and of afterhyperpolarizations (AHPs) in nociceptive A␦ and A␣/␤-fiber neurons . The time course of these changes was not known.Nerve growth factor (NGF) is upregulated in inflamed tissues and transported back to the dorsal root ganglia (DRGs) (Woolf et al., 1994). NGF is implicated in mediating inflammatory hyperalgesia because (1) administration of NGF leads to hyperalgesia in adult rats (Lewin et al

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Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons

Cited by 192 publications

References 69 publications

A 3.7 kb Fragment of the MouseScn10aGene Promoter Directs Neural Crest But Not Placodal Lineage EGFP Expression in a Transgenic Animal

A 3.7 kb Fragment of the MouseScn10aGene Promoter Directs Neural Crest But Not Placodal Lineage EGFP Expression in a Transgenic Animal

Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)

Time Course and Nerve Growth Factor Dependence of Inflammation-Induced Alterations in Electrophysiological Membrane Properties in Nociceptive Primary Afferent Neurons

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