Differential Neurotrophic Regulation of Sodium and Calcium Channels in an Adult Sympathetic Neuron

Ford, Christopher P.; Wong, Kenneth; Lu, Van B.; Chaves, E; Smith, Peter A.

doi:10.1152/jn.00966.2007

Cited by 10 publications

(7 citation statements)

References 83 publications

(109 reference statements)

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“…Both N-type and L-type currents are affected. Under the same in vitro conditions, TTX-sensitive and TTXR sodium currents are also increased by NGF (Lei et al 2001;Ford et al 2008), although delayed rectifier and M-type potassium currents remain unaffected.…”

Section: Ngf Regulates Ionic Currents In Sympathetic Neuronsmentioning

confidence: 87%

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

2009

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Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of nonpeptidergic nociceptors is also promoted by the NGFsignalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.

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Section: Ngf Regulates Ionic Currents In Sympathetic Neuronsmentioning

confidence: 87%

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

2009

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“…This has been reported for molecules such as phosphatidylinositol-bis-phosphate (PIP2) that alter channel conductance or gating (Zhang et al, 2003; Jia et al, 2007; Jia et al, 2008) or induce insertion of additional channels (Zhang et al, 2005). Activation of TrkA potentiates sodium current via phosphoinositide-3 kinase signaling and potentiates calcium current via ras-MAP kinase in bullfrog sympathetic neurons (Lei et al, 1997, 2001; Ford et al, 2008). Activation of p75 causes a ceramide-dependent regulation of sodium and potassium currents in rat sensory neurons via activation of G-protein-coupled receptors (Zhang et al, 2002; Zhang et al, 2006b).…”

Section: Discussionmentioning

confidence: 99%

“…Neurotrophins regulate calcium, sodium and potassium currents in sympathetic (Jia et al, 1999; Luther and Birren, 2006; Ford et al, 2008; Jia et al, 2008) and central nervous system neurons (Desai et al, 1999; Adamson et al, 2002; Wu and Yeh, 2005). Regulation of ionic currents may underlie neurotrophic regulation of firing patterns and function.…”

Section: Introductionmentioning

confidence: 99%

p75 and TrkA Signaling Regulates Sympathetic Neuronal Firing Patterns via Differential Modulation of Voltage-Gated Currents

Luther¹,

Birren²

2009

J. Neurosci.

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Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) act through the tropomyosin-related receptor tyrosine kinases (Trk) and the pan-neurotrophin receptor (p75) to regulate complex developmental and functional properties of neurons. While NGF activates both receptor types in sympathetic neurons, differential signaling through TrkA and p75 can result in widely divergent functional outputs for neuronal survival, growth, and synaptic function. Here we show that TrkA and p75 signaling pathways have opposing effects on the firing properties of sympathetic neurons, and define a mechanism whereby the relative level of signaling through these two receptors sets firing patterns via coordinate regulation of a set of ionic currents. We show that signaling through the p75 pathway causes sympathetic neurons to fire in a phasic pattern showing marked accommodation. Signaling through the NGF-specific TrkA, on the other hand, causes cells to fire tonically. Neurons switch rapidly between firing patterns, on the order of minutes to hours. We show that changes in firing patterns are caused by neurotrophin-dependent regulation of at least four voltage-gated currents: the sodium current and the M-type, delayed rectifier, and calcium-dependent potassium currents. Neurotrophin release, and thus receptor activation, varies among somatic tissues and physiological state. Thus, these data suggest that target-derived neurotrophins may be an important determinant of the characteristic electrical properties of sympathetic neurons and therefore regulate the functional output of the sympathetic nervous system.

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“…Interestingly, in contrast to the effects of axotomy and removal of NGF, which increase sodium current, long-term culture of frog sympathetic neurons with exogenous NGF has been shown to also increase sodium current (Lei et al, 2001; Ford et al, 2008). The explanation for these results remains to be determined, but it could be due to differential time-dependent effects of NGF signaling or to multiple interacting signaling factors lost through axotomy.…”

Section: Target-dependent Regulation Of Excitability and Neuronal mentioning

confidence: 99%

“…Long-term culture of frog sympathetic neurons in NGF leads to a dramatic increase in voltage-dependent sodium currents (Lei et al, 2001; Ford et al, 2008). This increase is blocked by the inhibitors wortmannin and LY294002, suggesting that NGF acts via TrkA activation of phosphatidylinositol 3-kinase signaling to mediate sodium channel up-regulation (Ford et al, 2008). Regulation of these currents is also blocked by the transcriptional inhibitors cordycepin and actinomycin-D, demonstrating a requirement for RNA transcription (Lei et al, 2001).…”

Section: Downstream Signaling Pathways In the Regulation Of Electrmentioning

confidence: 99%

Neurotrophins and target interactions in the development and regulation of sympathetic neuron electrical and synaptic properties

Luther

Birren

2009

Autonomic Neuroscience

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The electrical and synaptic properties of neurons are essential for determining the function of the nervous system. Thus, understanding the mechanisms that control the appropriate developmental acquisition and maintenance of these properties is a critical problem in neuroscience. A great deal of our understanding of these developmental mechanisms comes from studies of soluble growth factor signaling between cells in the peripheral nervous system. The sympathetic nervous system has provided a model for studying the role of these factors both in early development and in the establishment of mature properties. In particular, neurotrophins produced by the targets of sympathetic innervation regulate the synaptic and electrophysiological properties of postnatal sympathetic neurons. In this review we examine the role of neurotrophin signaling in the regulation of synaptic strength, neurotransmitter phenotype, voltage-gated currents and repetitive firing properties of sympathetic neurons. Together, these properties determine the level of sympathetic drive to target organs such as the heart. Changes in this sympathetic drive, which may be linked to dysfunctions in neurotrophin signaling, are associated with devastating diseases such as high blood pressure, arrhythmias and heart attack. Neurotrophins appear to play similar roles in modulating the synaptic and electrical properties of other peripheral and central neuronal systems, suggesting that information provided from studies in the sympathetic nervous system will be widely applicable for understanding the neurotrophic regulation of neuronal function in other systems.

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Differential Neurotrophic Regulation of Sodium and Calcium Channels in an Adult Sympathetic Neuron

Cited by 10 publications

References 83 publications

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

p75 and TrkA Signaling Regulates Sympathetic Neuronal Firing Patterns via Differential Modulation of Voltage-Gated Currents

Neurotrophins and target interactions in the development and regulation of sympathetic neuron electrical and synaptic properties

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