Changes In Excitability Properties Research Articles

Influence of age and gender in the sensory nerve fibers excitability.

ObjectivesTo assess the influence of age and gender on sensory nerve axonal excitability parameters.MethodsThirty‐three healthy subjects (21 women) were included, with a mean age of 34.6 (range 21–76). Median sensory nerve excitability measurements (index finger) were performed using the TRONDNF nerve excitability protocol of the QTRAC program.ResultsPeak sensory nerve action potential (SNAP) amplitude was significantly higher among women (27.1 vs. 9.2 μV; p = .022), and strength–duration time constant (SDTC) was significantly higher in men (0.7 vs. 0.5; p = .011), not dependent on age. Greater age was negatively correlated with resting I/V slope, not dependent on gender (r = –0.4; p = .024). No other changes in excitability properties with increasing age were found.ConclusionsPhysiological features like as age and gender do not have a relevant impact on sensory nerve excitability measurements, which can have implications regarding pharmacological treatments.

Changes in Excitability Properties of Ventromedial Motor Thalamic Neurons in 6-OHDA Lesioned Mice.

The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions has not be investigated at the cellular level. Such changes may well be expected because of homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-hydroxydopamine hydrochloride (6-OHDA)-treated adult mice. At a minimum of one month after 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily because of a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in the BG thalamocortical network in Parkinson’s disease.

Early discrimination of sensorimotor Guillain-Barré syndrome into demyelinating or axonal subtype by automated nerve excitability testing.

In the early stage of disease, differentiating acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor sensory axonal neuropathy (AMSAN) using only a conventional nerve conduction studies (NCS) may be difficult. We evaluated the differences in the motor axonal excitability properties of 16 cases of sensorimotor Guillain-Barré syndrome by nerve excitability testing (NET). The antiganglioside antibody assay and follow-up NCS resulted in 12 patients diagnosed as AIDP and 4 patients as AMSAN. Clinical and excitability parameters in each group were compared with those in 30 normal controls. Automated NET with threshold tracking techniques was used to calculate the strength-duration time constant (SDTC), threshold electrotonus (TE), current-threshold relationship (CTR), and recovery cycle (RC) of excitability. Except for subtle changes in excitability parameters, AIDP showed no definitive difference relative to normal controls. Comparison between AMSAN and normal controls also revealed no significant differences in the SDTC, TE, and CTR parameters. However, there were clear differences in some of the RC parameters: the relative refractory period was significantly longer in the AMSAN group than in the AIDP group (4.40 ± 1.11 vs. 3.09 ± 1.01 ms, mean ± SEM; p < 0.001), while superexcitability was significantly less prominent in the AMSAN group (-6.80 ± 10.30 vs. -26.48 ± 1.17%, mean ± SEM; p < 0.001). Our study identified that both AIDP and AMSAN were associated with subtle changes in excitability properties. Nonetheless, the prominent increase in refractoriness in AMSAN suggests the presence of a nodal conduction block.

Altered axonal excitability properties and nerve edema in POEMS syndrome

ObjectivePOEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome is a rare cause of demyelinating neuropathy with upregulation of vascular endothelial growth factor (VEGF). This study aimed to elucidate axonal excitability properties and their relation to VEGF levels and nerve edema in POEMS neuropathy. MethodsAxonal excitability measurement and nerve ultrasound were performed in the median nerve of 33 patients with POEMS syndrome. Serum VEGF levels were measured by ELISA. ResultsCompared with normal subjects (n=87), POEMS patients showed longer strength-duration time constant, fanning-out of threshold electrotonus curves, and greater threshold changes in a hyperpolarizing current–threshold relationship. Nerve ultrasound showed significant enlargement in POEMS patients. Serum VEGF levels and the extent of nerve edema partly correlated with nerve conduction slowing, as well as persistent sodium currents and inward rectification. ConclusionsIn POEMS syndrome, patterns of changes in excitability properties could suggest increased persistent sodium currents, and impaired potassium and inward rectifying channels. The findings were not consistent with depolarization due to nerve edema and compression ischemia. SignificanceIn addition to demyelination, nerve edema induced by upregulated VEGF, and upregulated inflammatory cytokines could modulate profiles of POEMS neuropathy.

P7-23 Multiple measures of axonal excitability in a mouse model of Kennedy disease

Objective: To examine motor nerve properties in a mouse model of spinal and bulbar muscular atrophy (SBMA), also known as Kennedy disease (KD) (i) to characterize excitability changes during disease progression and (ii) to determine how well the model reproduces the axonal excitability changes observed in SBMA patients. Methods.SBMA and Wild Type (WT) littermate male mice were recorded, under isoflurane anesthesia, between 3 and 20 months by stimulating the tibial branch of the sciatic motor nerve and recording compound muscle action potentials (CMAPs) from plantar muscles. As in patient studies, the multiple excitability program recorded stimulus-response, strengthduration and current-threshold relationships, threshold electrotonus and recovery-cycle. Since SBMA is a slowly progressive motor neuron pathology, data were divided in two groups (1) under 12 months when the mice are preor early symptomatic, and (2) over 12 months. Mutant and WT mice were compared. Results: In younger SBMA mice, no significant changes in excitability properties were observed compared to WT. In contrast, by 12 months, SBMA mice exhibited greater changes in response to depolarizing (p < 0.01) and hyperpolarizing (p < 0.001) currents, providing a fanning out appearance on the threshold electrotonus waveforms. Older SBMA mice also displayed smaller current/threshold gradients on the current-threshold relationship (p < 0.001). Some of these abnormalities were similar to those reported in patients with SBMA, but the change in current-threshold relationship was in the opposite direction. Furthermore, an increase in strength-duration time-constant, which was related to fasciculation frequency in the patients, was not significant in the SBMA mice. Conclusion: Although the SBMA mouse reproduces the motoneuron degeneration characteristic of SBMA and some of the axonal membrane changes, it is not a good model to explore the development of axonal hyperexcitability. Acknowledgments: This project was supported by MNDA. The authors gratefully acknowledge Mr Jim Dick for his assistance throughout this project.

Changes in excitability properties associated with axonal regeneration in human neuropathy and mouse Wallerian degeneration

Objective The aim of this study was to investigate changes in excitability properties associated with axonal regeneration in human neuropathy and a mouse Wallerian degeneration model. Methods Threshold tracking was used to measure axonal excitability indices such as strength–duration time constant (SDTC), threshold electrotonus, supernormality in median motor axons at the wrist of 13 patients with vasculitic neuropathy in their recovery phase, and in tibial motor axons at the ankle of mice with sciatic nerve crush. In the mouse model, excitability testing was performed 4, 8, 12, and 20 weeks after the nerve crush. Results In patients, there were longer SDTC, greater threshold changes at 0.2 ms in latent addition, and greater threshold changes in depolarizing and hyperpolarizing threshold electrotonus, compared with controls. The pattern of changes in excitability indices was similar to those in experimental nerve crush, in which the indices remained abnormal for 20 weeks after the crush. These changes suggest an increase in nodal persistent sodium currents, whereas multiple factors may also contribute to changes in excitability properties, such as axonal hyperpolarization, increased internodal resistance, and altered potassium currents. Conclusions Excitability properties in regenerating axons are characterized by increased nodal persistent currents with variable combination of changes in passive properties, membrane potential, and potassium currents. Significance Increased persistent sodium currents are potential reasons for positive symptoms in patients with axonal neuropathy. Sodium channel blockers could be considered a treatment option.

Early development of intrinsic and synaptic properties of chicken nucleus laminaris neurons

Onset of auditory brainstem responses in chickens takes place at about embryonic day 11/12 (E11/12). We investigated early development of neuronal properties of chicken nucleus laminaris neurons, the third-order auditory neurons critically involved in sound localization. Whole-cell patch recordings were performed in brainstem slices obtained at E10, E11, E12, E14, E16, and E18. At E18 neurons acquired an adult-like firing pattern in response to prolonged depolarizing current injections, with a single spike at the onset of the current injection followed by a plateau of membrane potential. At earlier ages, however, multiple spikes and/or subthreshold membrane potential oscillations were generated. We observed a >threefold reduction in input resistance from E10 to E18, and progressive changes in excitability properties, such as elevated threshold currents for spike generation, increased spike rising and falling rates, accompanied by reduced spike width and enhanced ability to follow high frequency inputs. Consistent with development of firing properties, the amplitude of voltage-gated potassium channel (Kv) currents increased by ∼threefold from E10 to E18, with a dramatic increase (∼ninefold) in the low threshold component. Excitatory postsynaptic potentials (EPSPs) were first recorded at E10, prior to and independent of the cochlear afferent inputs from the auditory nerve to the cochlear nucleus. EPSPs became markedly briefer in duration during the period studied. We conclude that the basic features of the key neuronal properties of NL neurons are well constructed during early development from E10 to E18.

Pacemaker activity resulting from the coupling with nonexcitable cells

Fibroblasts are nonexcitable cells that are sometimes coupled with excitable cells (cardiomyocytes). Due to a higher resting potential, these cells may act as a current source or sink and therefore disturb the electrical activity of the surrounding excitable cells. The possible occurrence of spontaneous pacemaker activity resulting from these electrotonic interactions was investigated in a theoretical model of two coupled cells as well as in a multicellular fiber model based on the Courtemanche kinetics. The results indicate that repeated spontaneous activations can be observed after an alteration in the activation and recovery properties of the sodium current (changes in excitability properties), provided that the difference in the resting potential as well as the coupling between the excitable and nonexcitable cells is sufficiently high. This may constitute a mechanism of focal sources triggering arrhythmias such as atrial fibrillation.

Changes in Excitable Properties of Olfactory Receptor Neurons Associated with Nerve Regenerationa

Changes in Excitable Properties of Olfactory Receptor Neurons Associated with Nerve Regeneration^a