Changes In Nerve Excitability Research Articles

Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in peripheral nerve excitability

To determine the effect of an established mutation of the beta1 subunit of Na(+) channels on nerve excitability, studies were undertaken in patients diagnosed with generalized epilepsy with febrile seizures plus (GEFS+). Multiple nerve excitability measurements were used to investigate the membrane properties of sensory and motor axons in five patients (aged 18-55 years) who were currently experiencing no seizures and were not on anticonvulsants. There was no history of paraesthesiae, fasciculation or cramps to suggest hyperexcitability of peripheral nerve axons. The median nerve was stimulated at the wrist, and compound muscle action potentials (CMAPs) were recorded from abductor pollicis brevis and the antidromic compound sensory nerve action potential (CSAPs) from digit 2. Stimulus-response behaviour, strength-duration time constant, threshold electrotonus, current-threshold relationship and the recovery of excitability following a supramaximal conditioning stimulus were recorded using threshold tracking. Compared with normal controls (n = 29), the axons of patients were of higher threshold. CMAPs and CSAPs were relatively small, although individual values remained within the normal ranges. Refractoriness and relative refractory period (markers of transient Na(+) channel function) were significantly reduced in GEFS+ patients with established mutations in SCN1B (P < 0.05), and strength-duration time constants (dependent on persistent Na(+) conductances) were reduced. It is suggested that, in peripheral nerve axons, the mutation underlying GEFS+ reduces the number of functioning Na(+) channels at the node of Ranvier and that this rather than any change in gating of individual channels dominates axonal excitability in these patients.

Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia.

Multiple nerve excitability measurements were used to investigate axonal membrane properties in patients with chronic renal failure (CRF). Nine patients were studied during routine haemodialysis therapy. The median nerve was stimulated at the wrist and compound muscle action potentials recorded from abductor pollicis brevis. Stimulus-response behaviour, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In six patients, sequential studies were performed before, during and after haemodialysis. All patients underwent standard electrolyte and renal function tests before and after haemodialysis. Before dialysis, there were significant abnormalities in axonal excitability: reduced superexcitability; increased accommodation to depolarizing and hyperpolarizing currents; and a steeper current-threshold relationship compared with normal controls. These excitability parameters are the most sensitive to membrane potential and the abnormalities, which were all reduced by haemodialysis, closely resembled those in normal axons depolarized by ischaemia. Before dialysis, the excitability parameters correlated significantly with serum potassium (range 4.3-6.1 mM), but not with other markers of renal dysfunction: patients with normal axonal resting potentials had normal serum potassium, although urea and creatinine were elevated. We conclude that nerves are depolarized in many CRF patients and that the depolarization is primarily due to hyperkalaemia.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates: V. Effects of electrode surface area

High rate intracochlear electrical stimulation at high intensities can induce significant reductions in the excitability of the auditory nerve as measured by a decrement in the amplitude of the electrically evoked auditory brainstem response (EABR). Such changes are primarily associated with stimulus induced neuronal activity, although direct current (DC) can also contribute. We examined the extent of stimulus induced change in auditory nerve excitability using large surface area platinum electrodes (‘high-Q’ electrodes). These electrodes have a surface area ∼70 times greater than standard Pt electrodes of the same geometric area, resulting in lower DC and charge density (charge/electrode surface area) for a common stimulus. Guinea pigs were bilaterally implanted with either high-Q or standard Pt electrodes, and unilaterally stimulated for 2 h using stimulus intensities of 12 dB or 20–30 dB above EABR threshold (0.34 μC/phase) at stimulus rates of 200, 400, or 1000 pulses per second (pps). EABRs were recorded before and following the acute stimulation. While there were significant reductions in EABR amplitudes and elevated EABR thresholds following stimulation at 12 dB above threshold using 400 and 1000 pps delivered to standard Pt electrodes, there were fewer or no significant changes in the post-stimulus EABR amplitude and threshold using high-Q electrodes under equivalent stimulus conditions. At a higher stimulus intensity (20–30 dB above EABR threshold), no reduction in EABR amplitude was observed at 200 pps for both stimulating electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. There was significantly greater EABR recovery following stimulation using high-Q electrodes compared with standard Pt electrodes at 400 ( P<0.05) and 1000 pps ( P<0.05). These data indicate that large surface area electrodes can significantly reduce stimulus induced changes in auditory nerve excitability, and may therefore have important clinical application.

Effect of pyrethroid (allethrin and fenvalerate) on excitability changes following nerve impulse.

Pyrethroid insecticides induce two different clinical symptoms. The difference has been reported to depend on the effect on the sodium channel opening time. We performed the present study to confirm this report by a double stimulation method. Allethrin (type I) 5 mg/kg and fenvalerate (type II) 1.5 kg/mg were injected into pentobarbital anesthetized rats. Tail nerve excitability was examined by a double stimulation method at from 4 msec to 40 msec intervals. The excitability was expressed as a percentage of the response to conditioned stimuli following supernormal stimuli to response to unconditioned stimuli. In control rats, the largest excitability was 94.6 +/- 19.2% at an 8 msec stimulus interval. After allethrin injection, we obtained two types of excitability changes. In some rats, supernormal excitability was present from 4 msec to 15 msec up to 120%. In other rats, the excitability was lower than that in the control from 4 msec to 15 msec. In fenvalerate treated rats, there was supernormal excitability from 4 msec to 40 msec. The peak of excitability was 122.4 +/- 35.3% at 10 msec. By double stimulation methods, we obtained characteristic nerve excitability changes in allethrin and fenvalerate treated rats after symptoms disappeared. These results showed that it should be possible to detect human nerve subclinical changes following lower doses or during chronic exposure.

Changes of nerve excitability and urinary deltamethrin in sprayers

The nerve excitability of median nerve as well as the urinary deltamethrin and its metabolite dibromovinyl-dimethyl-cyclopropane carboxylic acid (Br2A) were detected in 24 deltamethrin sprayers in an assessment of the exposure and effect of deltamethrin. Twenty-nine male, unexposed referents of the same age range were also selected. The urinary deltamethrin and its metabolite Br2A were detectable by GC and HPLC in the sprayers after exposure. The nerve excitability detected with an electromyograph and pairs of stimuli at variable intervals showed that there was a prolongation of supernormal period in median nerve of the exposed group after a 3-d spraying compared with that before spraying which became more significant 2 d after cessation of exposure. In the mean time, no change of supernormal period in the median nerve of reference group was found at the 3-d interval. Nearly half of the sprayers had a supernormal period prolonged by more than 4 ms after spraying, whereas nearly none of the reference group showed similar changes after repeated examinations. Although there was neither correlation between the nerve excitability changes and the urinary deltamethrin or Br2A excretion, nor was a case of acute deltamethrin poisoning diagnosed, the non invasive technique used for nerve excitability detection in this study seems to be valuable in studying deltamethrin toxicity on human.

Electrophysiologic deficits in peripheral nerve as a discriminator of early hexacarbon neurotoxicity.

To determine the extent of neurotoxicity of parenterally administered hexacarbons, male Sprague-Dawley rats were given either n-hexane or 2,5-hexanedione for 35 consecutive days. Electrophysiologic measurements showed a lengthening of the sciatic and sural nerve action potentials (slower conduction velocities) and increased refractory periods. These effects correlated with a shift in the nerve membrane sensitivity to potassium-induced depolarization. A similar effect can be induced by ouabain, an Na+, K+-ATPase inhibitor. These effects were seen with both n-hexane and 2,5-hexane-dione. Although the treated animals gained weight more slowly than controls, they showed no loss of motor function when tested behaviorally, and there were no signs of histopathology in the peripheral nerves. These results show that hexacarbons produce a neurotoxicity that can be demonstrated by changes in nerve excitability, prior to overt behavioral neurotoxicity. Furthermore, these electrophysiologic changes may be related to a hexacarbon-induced disruption of nerve-membrane ATPase activity.

Electrophysiologic changes associated with chronic administration of organophosphates.

Changes in the electrophysiologic activity of the rat sciatic nerve were examined after repeated dosing with either of two organophosphate insecticides, parathion, and trichlorfon. Although the parathion treated animals showed overt signs of systemic toxicity, there were no significant changes in any of the measured parameters of sciatic nerve excitability. Trichlorfon, on the other hand, produced dose-dependent changes in the duration, rise time, relative area, and refractory period of the sciatic nerve compound action potential. The observed changes indicated an increased excitability of the nerve. During the early development of these electrophysiologic changes there were no accompanying histologic changes in the nerve. This suggests that changes in nerve excitability may be a sensitive indicator of neurotoxicity, and that continued trichlorfon exposure may lead to a cumulative alteration in nerve function.

Laser lesions: changes in retinal excitability.

THE electroretinogram and optic tract potentials evoked by photic stimulation exhibit complex changes following the production of a chorioretinal lesion by a pulsed laser beam. Retinal function is not only permanently modified by the lesion, but its production is accompanied by temporary and possibly widespread changes in retino-optic nerve excitability.