Subthreshold membrane potential oscillation mediates the excitatory effect of norepinephrine in chronically compressed dorsal root ganglion neurons in the rat

Background Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage. Methods Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery. Results Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both Aalpha/beta and Adelta neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. Aalpha/beta neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in Adelta neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 Aalpha/beta and Adelta neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in Aalpha/beta L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in Aalpha/beta neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag. Conclusions These findings indicate that nerve injury-induced electrical instability is restricted to axotomized neurons and is absent in adjacent intact neurons.

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Effect of acetylcholine on membrane potential in toad dorsal root ganglion neurons and its underlying ionic basis

Journal of Tongji Medical University ◽

10.1007/bf02909085 ◽

1989 ◽

Vol 9 (4) ◽

pp. 210-215

Author(s):

Li Chao-ying ◽

Li Zhi-wang

Keyword(s):

Membrane Potential ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Ganglion Neurons ◽

Ionic Basis

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Nonlinear effects of hyperpolarizing shifts in activation of mutant Nav1.7 channels on resting membrane potential

Journal of Neurophysiology ◽

10.1152/jn.00898.2016 ◽

2017 ◽

Vol 117 (4) ◽

pp. 1702-1712 ◽

Cited By ~ 5

Author(s):

Mark Estacion ◽

Stephen G. Waxman

Keyword(s):

Membrane Potential ◽

Dorsal Root Ganglion ◽

Sodium Channel ◽

Dorsal Root ◽

Voltage Dependence ◽

Dorsal Root Ganglion Neurons ◽

Resting Membrane Potential ◽

Dynamic Clamp ◽

Drg Neurons ◽

Ganglion Neurons

The Nav1.7 sodium channel is preferentially expressed within dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function mutations that cause the painful disorder inherited erythromelalgia (IEM) shift channel activation in a hyperpolarizing direction. When expressed within DRG neurons, these mutations produce a depolarization of resting membrane potential (RMP). The biophysical basis for the depolarized RMP has to date not been established. To explore the effect on RMP of the shift in activation associated with a prototypical IEM mutation (L858H), we used dynamic-clamp models that represent graded shifts that fractionate the effect of the mutation on activation voltage dependence. Dynamic-clamp recording from DRG neurons using a before-and-after protocol for each cell made it possible, even in the presence of cell-to-cell variation in starting RMP, to assess the effects of these graded mutant models. Our results demonstrate a nonlinear, progressively larger effect on RMP as the shift in activation voltage dependence becomes more hyperpolarized. The observed differences in RMP were predicted by the “late” current of each mutant model. Since the depolarization of RMP imposed by IEM mutant channels is known, in itself, to produce hyperexcitability of DRG neurons, the development of pharmacological agents that normalize or partially normalize activation voltage dependence of IEM mutant channels merits further study. NEW & NOTEWORTHY Inherited erythromelalgia (IEM), the first human pain disorder linked to a sodium channel, is widely regarded as a genetic model of neuropathic pain. IEM is produced by Nav1.7 mutations that hyperpolarize activation. These mutations produce a depolarization of resting membrane potential (RMP) in dorsal root ganglion neurons. Using dynamic clamp to explore the effect on RMP of the shift in activation, we demonstrate a nonlinear effect on RMP as the shift in activation voltage dependence becomes more hyperpolarized.

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