Effects of central or peripheral axotomy on membrane properties of sensory neurones in the petrosal ganglion of the cat.

Gallego, Roberto; Ivorra, Isabel; Morales, Andrés

doi:10.1113/jphysiol.1987.sp016724

Cited by 57 publications

(41 citation statements)

References 37 publications

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“…These changes include altered excitability of the somadendritic compartment and axon initial segment (17,19), which involves Na-dependent electrogenesis (22,23). While these early experiments were interpreted as suggesting a shift in vectorial transport of channels in axotomized neurons (21,24), our results indicate that an altered pattern of gene expression contributes to the electrophysiological changes.…”

Section: Discussionmentioning

confidence: 60%

“…Altered neuronal excitability has been demonstrated following axonal transection (17)(18)(19) and may underlie abnormal DRG bursting associated with pain syndromes (9,20). Abnormal somatodendritic excitability following axotomy is Na dependent (21,22), and it has been suggested that this is due to a shift, following axotomy, in vectorial transport of Na channels (23,24).…”

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confidence: 99%

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Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

Dib‐Hajj

Black²,

Felts

et al. 1996

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

223

127

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Spinal sensory (dorsal root ganglion; DRG) neurons display slowly inactivating, tetrodotoxin-resistant (TTX-R), and rapidly inactivating, TTX-sensitive (TTX-S) Na currents. Attenuation of the TTX-R Na current and enhancement of TTX-S Na current have been demonstrated in cutaneous afferent DRG neurons in the adult rat after axotomy and may underlie abnormal bursting. We show here that steady-state levels of transcripts encoding the ␣-SNS subunit, which is associated with a slowly inactivating, TTX-R current when expressed in oocytes, are reduced significantly 5 days following axotomy of DRG neurons, and continue to be expressed at reduced levels, even after 210 days. Steady-state levels of ␣-III transcripts, which are present at low levels in control DRG neurons, show a pattern of transiently increased expression. In situ hybridization using ␣-SNS-and ␣-IIIspecific riboprobes showed a decreased signal for ␣-SNS, and an increased signal for ␣-III, in both large and small DRG neurons following axotomy. Reduced levels of ␣-SNS may explain the selective loss of slowly inactivating, TTX-R current. The abnormal electrophysiological properties of DRG neurons following axonal injury thus appear to ref lect a switch in Na channel gene expression.Multiple voltage-gated Na currents with different kinetics and voltage dependence have been observed in spinal sensory (dorsal root ganglion; DRG) neurons, which relay signals from peripheral receptors into the central nervous system. These include rapidly inactivating, TTX-sensitive (TTX-S) currents, and slowly inactivating, TTX-resistant (TTX-R) Na currents (1-4). Interplay of the currents influences the firing properties of DRG neurons (5-8) and may contribute to ectopic generation of action potentials in these cells following injury to their axons within peripheral nerves (9).Neural Na channels are heterotrimers composed of an ␣ subunit and two ␤ subunits, ␤1 and ␤2 (10 -12). Nucleotide sequence variation allows identification of ␣ subunits within single neurons by in situ hybridization (ISH) or in a cDNA pool using reverse transcriptase-PCR (RT-PCR) and restriction enzyme polymorphism (REP). ISH and RT-PCR͞ REP analyses have demonstrated that transcripts of multiple channel ␣ subunits, including ␣-I, ␣-II, NaG, Na6, and hNE (PN1), are expressed in single DRG neurons (13). The expression of these transcripts may explain the diversity of Na currents in these cells. Recently, a novel ␣ subunit , also termed PN3 (15)] was identified and found to be restricted to peripheral sensory neurons. ␣-SNS contains a serine at a site within domain I which has been shown, by site-directed mutagenesis, to confer resistance to TTX in the cardiac muscle Na channel (16). Expression of ␣-SNS cRNA produces a slowly inactivating, TTX-R current in Xenopus oocytes, suggesting that ␣-SNS is responsible for a TTX-R Na current in DRG neurons (14,15).Altered neuronal excitability has been demonstrated following axonal transection (17-19) and may underlie abnormal DRG bursting associated with pain...

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

Dib‐Hajj

Black²,

Felts

et al. 1996

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

223

127

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“…However, the changes in electrophysiological properties after axotomy are variable and depend on the type of neuron as well as the organism. For example, in cat and rat, injured dorsal root ganglia (DRG) neurons display a decrease in the amplitude and duration of the afterhyperpolarization (AHP) (Gallego et al, 1987;Sapunar et al, 2005), whereas the duration of AHPs in injured DRG neurons in hamster (Gurtu and Smith, 1988) or mouse (Liu et al, 2002) does not change.…”

Section: Introductionmentioning

confidence: 99%

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

McClellan¹,

Kovalenko²,

Benes³

et al. 2008

J. Neurosci.

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In larval lamprey, hemitransections were performed on the right side of the rostral spinal cord to axotomize ipsilateral reticulospinal (RS) neurons. First, at short recovery times (2-3 weeks), uninjured RS neurons contralateral to hemitransections fired a smooth train of action potentials in response to sustained depolarization, whereas axotomized neurons fired a single short burst or short repetitive bursts. For uninjured RS neurons, the afterpotentials of action potentials had three components: fast afterhyperpolarization (fAHP), afterdepolarizing potential (ADP), and slow AHP (sAHP) that was attributable to calcium influx via high-voltage-activated (HVA) (N-and P/Q-type) calcium channels and calcium-activated potassium channels (SKKCa). For axotomized RS neurons, the fAHP was significantly larger than for uninjured neurons, and the ADP and sAHP were absent or significantly reduced. Second, at relatively long recovery times (12-16 weeks), axotomized RS neurons displayed firing patterns and afterpotentials that were similar to those of uninjured neurons. Third, mRNA levels of lamprey HVA calcium and SKKCa channels in axotomized RS neurons were significantly reduced at short recovery times and restored at long recovery times. Fourth, blocking calcium channels in uninjured RS neurons resulted in altered firing patterns that resembled those produced by axotomy. We demonstrated previously that lamprey RS neurons in culture extend neurites, and calcium influx results in inhibition of neurite outgrowth or retraction. Together, these results suggest that the downregulation of Ca 2ϩ channels in axotomized RS neurons, and the associated reduction in calcium influx, maintain intracellular calcium levels in a range that is permissive for axonal regeneration.

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“…Excitability and Na current density are altered in neurons after axonal injury (22)(23)(24)(25). After axotomy, rat DRG neurons display dramatic changes in their TTX-R and TTX-S Na currents and in their Na channel mRNA profile; these changes include an attenuation of TTX-R and enhancement of TTX-S Na currents (21, 26), down-regulation of SNS͞PN3 transcripts and up-regulation of ␣III transcripts (20), and moderate elevation in the levels of ␣I and ␣II mRNAs (27).…”

Section: Introductionmentioning

confidence: 99%

NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy

Dib‐Hajj

Tyrrell

Black

et al. 1998

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

469

306

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Although physiological and pharmacological evidence suggests the presence of multiple tetrodotoxinresistant (TTX-R) Na channels in neurons of peripheral nervous system ganglia, only one, SNS͞PN3, has been identified in these cells to date. We have identified and sequenced a novel Na channel ␣-subunit (NaN), predicted to be TTX-R and voltage-gated, that is expressed preferentially in sensory neurons within dorsal root ganglia (DRG) and trigeminal ganglia. The predicted amino acid sequence of NaN can be aligned with the predicted structure of known Na channel ␣-subunits; all relevant landmark sequences, including positively charged S4 and pore-lining SS1-SS2 segments, and the inactivation tripeptide IFM, are present at predicted positions. However, NaN exhibits only 42-53% similarity to other mammalian Na channels, including SNS͞PN3, indicating that it is a novel channel, and suggesting that it may represent a third subfamily of Na channels. NaN transcript levels are reduced significantly 7 days post axotomy in DRG neurons, consistent with previous findings of a reduction in TTX-R Na currents. The preferential expression of NaN in DRG and trigeminal ganglia and the reduction of NaN mRNA levels in DRG after axonal injury suggest that NaN, together with SNS͞PN3, may produce TTX-R currents in peripheral sensory neurons and may inf luence the generation of electrical activity in these cells.Voltage-gated Na channels in rat brain are composed of three subunits: the pore-forming ␣-subunit (260 kDa), which is sufficient to generate Na current flow across the membrane, and two auxiliary subunits, ␤1 (36 kDa) and ␤2 (33 kDa), which can modulate the properties of the ␣-subunit (1, 2). Nine distinct ␣-subunits have been identified in the rat (ref. 3 and references therein, refs. 4-6), and homologues have been cloned from various mammalian species, including humans (3). Specific ␣-subunits are expressed in a tissue-and developmentally specific manner (7). Aberrant expression patterns or mutations of voltage-gated sodium channel ␣-subunits underlie a number of human and animal disorders (1, 8-11).Multiple voltage-gated Na currents, some tetrodotoxinsensitive (TTX-S) and others TTX-resistant (TTX-R) (12-15), have been observed in dorsal root ganglia (DRG) neurons, which express multiple Na channel ␣-subunit mRNAs (16). The complex Na current profile in DRG neurons influences their excitability (13,(17)(18)(19) and may contribute to ectopic or spontaneous firing in these cells after injury to their axons (8,20,21).Excitability and Na current density are altered in neurons after axonal injury (22)(23)(24)(25). After axotomy, rat DRG neurons display dramatic changes in their TTX-R and TTX-S Na currents and in their Na channel mRNA profile; these changes include an attenuation of TTX-R and enhancement of TTX-S Na currents (21, 26), down-regulation of SNS͞PN3 transcripts and up-regulation of ␣III transcripts (20), and moderate elevation in the levels of ␣I and ␣II mRNAs (27). Inflammatory modulators also up-regulate TTX-R c...

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Effects of central or peripheral axotomy on membrane properties of sensory neurones in the petrosal ganglion of the cat.

Cited by 57 publications

References 37 publications

Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

Down-regulation of transcripts for Na channel α-SNS in spinal sensory neurons following axotomy

Spinal Cord Injury Induces Changes in Electrophysiological Properties and Ion Channel Expression of Reticulospinal Neurons in Larval Lamprey

NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy

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