Neuromodulation of Na+ channels: An unexpected form of cellular platicity

Cantrell, Angela R.; Catterall, William A.

doi:10.1038/35077553

Cited by 318 publications

(293 citation statements)

References 111 publications

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“…An alternative is the recruitment of a kinase to the channel complex and the subsequent phosphorylation of the channel. Phosphorylation of sodium channels by PKA and PKC has been shown to either increase or decrease the peak current amplitude, depending on the channel isoform (Fitzgerald et al, 1999;Cantrell and Catterall, 2001;Vijayaragavan et al, 2004). Another alternative is that the binding of FHF2B to the C terminus may increase the probability of channel opening upon depolarization.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Wittmack¹,

Rush²,

Craner³

et al. 2004

J. Neurosci.

125

174

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Voltage-gated sodium channels interact with cytosolic proteins that regulate channel trafficking and/or modulate the biophysical properties of the channels. Na v 1.6 is heavily expressed at the nodes of Ranvier along adult CNS and PNS axons and along unmyelinated fibers in the PNS. In an initial yeast two-hybrid screen using the C terminus of Na v 1.6 as a bait, we identified FHF2B, a member of the FGF homologous factor (FHF) subfamily, as an interacting partner of Na v 1.6. Members of the FHF subfamily share ϳ70% sequence identity, and individual members demonstrate a cell-and tissue-specific expression pattern. FHF2 is abundantly expressed in the hippocampus and DRG neurons and colocalizes with Na v 1.6 at mature nodes of Ranvier in myelinated sensory fibers in the dorsal root of the sciatic nerve. However, retinal ganglion cells and spinal ventral horn motor neurons show very low levels of FHF2 expression, and their axons exhibit no nodal FHF2 staining within the optic nerve and ventral root, respectively. Thus, FHF2 is selectively localized at nodes of dorsal root sensory but not ventral root motor axons. The coexpression of FHF2B and Na v 1.6 in the DRG-derived cell line ND7/23 significantly increases the peak current amplitude and causes a 4 mV depolarizing shift of voltage-dependent inactivation of the channel. The preferential expression of FHF2B in sensory neurons may provide a basis for physiological differences in sodium currents that have been reported at the nodes of Ranvier in sensory versus motor axons.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Wittmack¹,

Rush²,

Craner³

et al. 2004

J. Neurosci.

125

174

View full text Add to dashboard Cite

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“…PKC activity is elevated in spinal cord tissue from hSOD1 G93A mice and from human ALS patients (Hu et al, 2003a,b). PKC-mediated phosphorylation of Na ϩ channels increases channel open time and decreases channel inactivation (Numann et al, 1991;Cantrell and Catterall, 2001), producing an increased PC Na (Astman et al, 1998). Thus, in hSOD1 G93A mice, oxidative stress and Ca 2ϩ entry driven by activity-dependent activation of voltage-gated Ca 2ϩ channels could activate PKC, increasing PC Na and motoneuron excitability.…”

Section: Msod1mentioning

confidence: 99%

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Zundert¹,

Peuscher²,

et al. 2008

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Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1 G93A mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1 G93A mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)-P10 hSOD1 G93A mice displayed hyperexcitability, increased persistent Na ϩ current (PC Na ), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1 G93A mouse, and are present 2-3 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10 -P12). Furthermore, in vivo viral-mediated GFP (green fluorescent protein) overexpression in hSOD1 G93A HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PC Na and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS.

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“…Clearly, sodium currents participate in multiple aspects of membrane excitability (Crill, 1996;Cantrell and Catterall, 2001) to shape neuronal discharge. Moreover, modification of these currents as a basis for certain pathophysiological conditions has now been established (Ashcroft, 2000).…”

Section: Slow Inactivation and Burst Terminationmentioning

confidence: 99%

Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

Enomoto¹,

Han²,

Hsiao³

et al. 2006

J. Neurosci.

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Subthreshold sodium currents are important in sculpting neuronal discharge and have been implicated in production and/or maintenance of subthreshold membrane oscillations and burst generation in mesencephalic trigeminal neurons (Mes V). Moreover, recent data suggest that, in some CNS neurons, resurgent sodium currents contribute to production of high-frequency burst discharge. In the present study, we sought to determine more directly the participation of these currents during Mes V electrogenesis using the action potentialclamp method. In postnatal day 8 -14 rats, the whole-cell patch-clamp method was used to record sodium currents by subtraction in response to application of TTX in voltage-clamp mode using the action potential waveform as the command protocol. We found that TTX-sensitive sodium current is the main inward current flowing during the interspike interval, compared with the h-current (I h ) and calcium currents. Furthermore, in addition to the transient sodium current that flows during the upstroke of action potential, we show that resurgent sodium current flows at the peak of afterhyperpolarization and persistent sodium current flows in the middle of the interspike interval to drive high-frequency firing. Additionally, transient, resurgent, and persistent sodium current components showed voltage-and time-dependent slow inactivation, suggesting that slow inactivation of these currents can contribute to burst termination. The data suggest an important role for these components of the sodium current in Mes V neuron electrogenesis.

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Neuromodulation of Na+ channels: An unexpected form of cellular platicity

Cited by 318 publications

References 111 publications

Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

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Neuromodulation of Na+ channels: An unexpected form of cellular platicity

Cited by 318 publications

References 111 publications

Fibroblast Growth Factor Homologous Factor 2B: Association with Nav1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Fibroblast Growth Factor Homologous Factor 2B: Association with Nav1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

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Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons

Fibroblast Growth Factor Homologous Factor 2B: Association with Na_v1.6 and Selective Colocalization at Nodes of Ranvier of Dorsal Root Axons