Axonal Conduction Block Research Articles

Chronic inflammatory demyelinating polyneuropathy (CIDP) with ophthalmoplegia: a case with asymmetric limb weakness and high titers of anti‐GM1 antibody

We describe a patient with high titers of anti‐GM1 antibody but not anti‐GQ1b antibody who had recurrent asymmetric limb weakness with little sensory deficit and developed left abducens palsy. Nerve conduction study showed multifocal conduction block or dispersion of motor and sensory axons in the same mixed nerve. Pulse steroid followed by oral predonisolone treatment rapidly resolved his symptoms.

WS-10-1 The development of conduction block in human axons

WS-10-1 The development of conduction block in human axons

COMPARISON OF MULTIPLE FREQUENCY VIBROMETRY TESTING AND SENSORY NERVE CONDUCTION MEASURES IN SCREENING FOR CARPAL TUNNEL SYNDROME IN AN INDUSTRIAL SETTING

The value of vibrometry in the evaluation of carpal tunnel syndrome is controversial. Several investigators have suggested that vibrometry screening with multiple frequencies would improve the correlation and increase the sensitivity when screening for carpal tunnel syndrome. One hundred sixty-nine industrial workers from two manufacturing plants in southern Michigan were screened for median nerve impairment using both vibrometry (seven frequencies, 8-500 Hz) and electrophysiologic testing in each hand. The vibratory threshold at each frequency, as well as composite measures-Jetzer index and negative sums, were compared with electrophysiologic measures of amplitude and latency. The individual frequencies and the Jetzer index correlated with median sensory latency, but the relationships were weak (r = 0.22 to 0.32). Only at the lower frequencies (8, 16, and 32 Hz) did the vibratory threshold correlate with sensory amplitude; correlation ranged from 0.187 to 0.303. Vibration threshold sensation is most closely related to axonal loss or conduction block, but the earliest finding in carpal tunnel syndrome is that of demyelination; thus we would not expect an abnormal vibratory threshold with mild carpal tunnel syndrome. These results support this interpretation and suggest that vibratory screening for early carpal tunnel syndrome is not effective.

Improvement by diazepam of neuromuscular transmission blocked by anticholinesterase agents in mouse diaphragms

Effects of diazepam on the neuromuscular transmission blocked by neostigmine were studied in isolated mouse phrenic nerve-diaphragm preparations. Diazepam, in the absence of neostigmine, had no significant effect on the neuromuscular transmission at concentrations lower than 100 μM, except to enhance muscle contractility. Single and train pulses-evoked endplate potentials (e.p.p.s) and miniature e.p.p.s (m.e.p.p.s) were also unaffected. At concentrations of 175 μM or higher, diazepam caused an axonal conduction block. However, neostigmine-induced twitch potentiation, spontaneous fasciculation and tetanic fade were antagonized by diazepam at 3.5–35 μM. Diazepam did not decrease the amplitude of neostigmine-augmented e.p.p.s and m.e.p.p.s but slightly reduced their decay time. The incidence of regenerative depolarization of endplates induced by repetitive stimulation in the presence of neostigmine, was decreased from 92% to 35% junctions and the duration shortened from 650 ms to 230 ms. The amplitude of train e.p.p.s was increased. It is suggested that diazepam reverses the muscle paralysis induced by anticholinesterase agents by inhibiting the regenerative release of acetylcholine.

Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve

Endothelin (ET) is a potent vasoconstrictor peptide that may have pathophysiological roles in the microcirculation of the peripheral nervous system. We examined the local action of epineurial ET-1 on sciatic endoneurial blood flow using serial hydrogen clearance measurements in anesthetized, paralyzed, and ventilated Sprague-Dawley rats. In separate rats, we made serial measurements of sciatic motor multifiber conduction before and then after application of epineurial ET (saline on contralateral nerve) 2 and 24 h and 4 and 7 days later. Epineurial bathing solutions of ET increased microvascular resistance and reduced local endoneurial blood flow in a dose-responsive fashion with a half-maximum effective concentration of 10(-8) M. Maximum vasoconstriction at 10(-6) M ET was associated with a fall in endoneurial blood flow from 18.7 (pre-ET) to 7.2 ml x 100 g-1 x min-1. Epineurial norepinephrine (10(-7) to 10(-10) M) also resulted in vasoconstriction, but of lesser degree. Pretreatment with intraperitoneal nimodipine, a dihydropyridine Ca2+ channel antagonist, but not phentolamine, prevented the vasoconstrictive action of ET. Three of eight animals developed temporary but complete axonal conduction block at the site of ET administration (10(-5) M) and four others had partial conduction block. Contralateral saline-treated sciatic fibers were unaffected. Local ET action on extrinsic epineurial microvessels results in reversible ischemia of the underlying endoneurium that may be associated with conduction block. ET's action is more potent than norepinephrine and appears dependent on L-type voltage-gated Ca2+ channels.

Quantitation of axon loss and conduction block in acute radial nerve palsies.

Eleven acute radial nerve palsies were examined between 3 days and 14 weeks following the onset of the neuropathy. Our objective was to quantify the relative extent of axon loss and conduction block in radial motor fibers supplying the extensor and abductor pollicis longus (EPL/APL) muscles. In 10 of 11 cases, conduction block exceeded axon loss. Maximum motor and sensory conduction velocities were normal distal to the spiral groove, suggesting that the larger myelinated fibers were not selectively involved in this acute neuropathy. The localization of the conduction block and slowing was, in every case, across the spiral groove. This method provides a relatively simple way of assessing the approximate contributions of axon loss and conduction block, and fits well with the early and usually complete clinical recovery in these cases.

Laser microbeam axotomy and conduction block show that electrical transmission at a central synapse is distributed at multiple contacts

Touch (T) sensory neurons in the leech innervate defined regions of skin and synapse on other neurons, including other T cells, within the ganglionic neuropil. The cells' receptive fields in the periphery are comprised of a central region, innervated by thick axons, and adjoining regions (minor fields) innervated by thinner axons. Secondary branches, known to be sites of synapses, emerge from the thinner and thicker axons. Pairs of T cells appear to make up to 200 separate contacts distributed within the neuropil. When the T cell is hyperpolarized, as occurs during natural stimulation of the cell, action potentials generated in the minor field and travelling into the ganglion along the thin axons may fail to conduct at central branch points. Evidence is presented, using axon conduction block and laser axotomy of cells filled with 6-carboxy-fluorescein, that synapses between separate groups of branches can function independently. Thus, selective activation of branches of the thin anterior axon produced a synaptic potential 36 +/- 6% of control amplitude, which was consistent with counts of 39 +/- 6% of contacts made by these branches. Laser axotomy of postsynaptic neurons showed that the anterior contacts indeed made the principal or only contacts activated during anterior conduction block. The results show that conduction block can modulate transmission within the ganglion, and it operates by silencing particular contacts between cells.

Effect of 4-aminopyridine on axonal conduction-block in chronic spinal cord injury

The spinal cords of 18 anesthetized cats were injured by standardized contusion. The animals were maintained for 4–16 months, then the thoracic spinal cord was isolated in vitro at 25°C. Microelectrode recordings were made from single axons conducting through the lesion in ventral and lateral tracts. On warming the tissue, action potential conduction was found to block at temperatures below 36°C in 29% of 129 axons tested. Of 17 axons in which it was possible to demonstrate a block below physiological temperature, apply 0.1–1 mM 4-AP, wait for 10 min and test conduction again, 7 showed increases in blocking temperature and 4 of these were restored to conduction above 37°C. The other 10 fibers showed no improvement in blocking temperature. 4-AP also increased the spontaneous activity of axons. It was concluded that 4-AP may eventually be useful in chronic spinal cord injuries, because it improves safety factor in some axons and increases excitability in others, which may compensate to some extent for the reduction in density of projections through the lesion.

Neuromuscular block by verapamil and diltiazem and inhibition of acetylcholine release

The effects of Ca 2+-channel antagonists, verapamil, diltiazem and nifedipine, on the neuromuscular transmission were studied in the isolated mouse phrenic nerve-diaphragm preparations. All 3 drugs increased the twitch response evoked by direct single stimulation at 10–100 μM. The neuromuscular transmission at 0.1 Hz was blocked by verapamil and diltiazem, but not by nifedipine, only at very high concentrations (⩾100 μM). In the time course of block, no endplate potential (e.p.p.) could be recorded, whenever the junction failed to elicit an action potential, suggesting that the block is due to an axonal conduction failure. Conduction block became apparent in both axon and muscle at low concentrations (>10 μM) of verapamil and diltiazem at 100 Hz. When the safety margin of neuromuscular transmission was reduced by tubocurarine or low Ca 2+ plus high Mg 2+, verapamil and diltiazem, but not nifedipine, reduced the single twitch response to nerve stimulation at concentrations that did not cause axon conduction block. The inhibition was dependent on the frequency of nerve stimulation, enhanced by low-Ca 2+ and antagonized by high-Ca 2+. Verapamil (50 μM) inhibited the mean amplitude of the median size miniature e.p.p. by only8 %, whereas it increased the frequency by 4–5 fold and the proportion of both small and giant miniature e.p.p.s. The e.p.p. amplitude was inhibited by verapamil by about 67% in low-Ca 2+ media and by about 38% in normal Tyrode. Similar but somewhat lesser effect was obtained with diltiazem. It is concluded that verapamil and diltiazem, but not nifedipine, inhibit the transmitter release. This effect in normal Tyrode, however, is largely due to an inhibition of Na +-channel. An inhibition of Ca 2+-channel may be involved in low-Ca 2+ media.

The actions of phenol and pentachlorophenol (PCP) on axonal conduction, ganglionic synaptic transmission, and the effect of ph changes

1. A comparison of phenol, pentachlorophenol (PCP) and procaine effects on axonal conduction were studied in vitro in the sciatic nerves of toad. PCP and procaine were respectively 6.3 and 3.15 times more potent than phenol in blocking axonal conduction. 2. Effects of PCP on synaptic transmission were studied vitro in the eighth sympathetic ganglion of toad. 3. Axonal conduction block and synaptic transmission block by phenol was reversible, but not that by PCP. 4. When the PCP ionization was increased, a lesser per cent reached the site of action, reducing its capacity to block the axonal conduction and ganglionic transmission. 5. PCP plus, 3,4-Diaminopyridine (3,4-DAP) decreased synaptic transmission block from postganglionic compound action potential (CAP) responses to supramaximal preganglionic stimulation.

Lack of Size-Related Differential Sensitivity to Equilibrium Conduction Block among Mammalian Myelinated Axons Exposed to Lidocaine

This study sought to evaluate the sensitivity of individual, relatively thick myelinated axons of mammalian nerve to equilibrium conduction block by lidocaine, and to compare this to the incidence of conduction block previously measured in individual thinner myelinated axons. The incidence of conduction block by lidocaine 0.3 and 0.6 mM (8.1-16.2 mg/dl) was determined on 35 individual axons in dissected filaments of rabbit recurrent laryngeal nerve (RLN) in which the control conduction velocity ranged from 28 to 77 m/sec. Thirty-four axons (97%) remained excitable in lidocaine 0.3 mM; 2 axons (6%) remained excitable in lidocaine 0.6 mM. These proportions did not differ significantly (P greater than 0.2) from those in thinner axons of vagus, either in comparisons with previous data from extracellular recordings or with new data from filament recordings. The results imply that differential blocks observed under clinical conditions probably depend on factors other than a size-related difference in the minimal equilibrium blocking concentration among myelinated axons. Equilibrium depression of the amplitude of RLN compound action potentials by lidocaine 0.3 and 0.6 mM was disproportionately great relative to the incidence of equilibrium conduction block in individual axons, confirming that depression of the compound action potential is not a reliable measure of nerve conduction block.

Withdrawal Reflex and Conduction Block in the Giant Axons of a Sabellid Worm (Pseudopotamilla Occelata)

ABSTRACT Body contraction in the sabellid worm, Pseudopotamilla occelata, during the rapid withdrawal reflex occurred only in the anterior half of the body. End-to-end shortening was never observed. The longitudinal muscles are well-developed in the anterior half, and poorly developed in the posterior half. Conduction of action potentials along the giant axons was blocked at the midbody, and was responsible for the anteriorly restricted body contraction. Electrophysiological and histological studies excluded the possibility that conduction block resulted from a safety factor attributable to the special geometry of the axons. Current injection across the giant axon membrane in the region of the conduction block indicated that changes in the properties of the membrane were responsible for the conduction block.

Evolution of axonal swellings in cats intoxicated with β,β′-iminodipropionitrile (IDPN): An electrophysiological and morphological study

β,β′-Iminodipropionitrile (IDPN) causes formation of axonal swellings in the proximal internodes of spinal motor axons. The swellings enlarge and demyelinate with the progression of the neuropathy. The correlation between axonal swellings and electrophysiologic function of motoneurons was examined in cats 2 to 35 days after initial administration of IDPN. Morphologic changes in intraspinal motor axons, occasionally observed 2 days after the first injection, became progressively more evident at later times, with enlargement at the first internode in some axons and appearance of fusiform or balloon-like axonal swellings. At 7 days axonal swellings were infrequently observed and the main structural feature was a reduction in myelin thickness in affected nerve fibers. Despite scant histopathologic changes, motoneuron action potential discharge at this time was significantly altered in latency to onset of spike and rate of rise. Abnormal motoneuron firing patterns were observed at this time. As the neuropathy progressed, both the frequency of occurrence and the size of axonal swellings increased markedly but at no time was there morphologic evidence of chromatolysis. At 14 and 35 days, (after two or five IDPN injections) action potential discharge became further altered in latency to spike onset, rate of rise, initial segment conduction time and somal-dendritic threshold. The incidence of repetitive firing increased and axonal conduction block was observed in several motoneuron recordings. The electrophysiologic changes closely resemble those reported in chromatolytic motoneurons after axotomy. The axonal swellings induced by IDPN may produce an axotomy-like condition which becomes more prominent as the neuropathy progresses but without morphologic evidence of chromatolysis.

Maturation of mammalian myelinated fibers: changes in action-potential characteristics following 4-aminopyridine application.

Maturation of mammalian myelinated fibers: changes in action-potential characteristics following 4-aminopyridine application.

AN INHIBITORY EFFECT OF ETHANOL ON ADRENERGIC NEUROMUSCULAR TRANSMISSION IN THE GUINEA-PIG VAS DEFERENS

Effects of ethanol on adrenergic neuromuscular transmission were investigated in the isolated vas deferens of the guinea-pig. The contractile responses to adrenergic nerve stimulation were depressed by ethanol in a concentration-dependent, reversible manner at a concentration range between 25 and 500 mM. Ethanol also depressed the contractions induced by exogenous noradrenaline. The resting membrane potentials recorded intracellularly from the smooth muscle cells were not affected by the alcohol. The excitatory junction potentials (EJPs) evoked by nerve stimulation decreased in amplitude, but the facilitation phenomena observed with repetitive stimulation remained unaltered. Ethanol slightly increased the frequency of the spontaneous EJPs, but decreased their amplitude. The extracellularly recorded action potentials from the small sympathetic nerve bundles innervating the vas deferens were suppressed by high concentrations of ethanol (more than 200 mM). These results indicate that ethanol inhibits adrenergic neuromuscular transmission in the vas deferens probably through depressing the sensitivity of the postsynaptic membrane to the transmitter and a block of axonal conduction in the presynaptic nerve terminals.

An inhibitory effect of ethanol on adrenergic neuromuscular transmission in the guinea-pig vas deferens.

Effects of ethanol on adrenergic neuromuscular transmission were investigated in the isolated vas deferens of the guinea-pig. The contractile responses to adrenergic nerve stimulation were depressed by ethanol in a concentration-dependent, reversible manner at a concentration range between 25 and 500 mM. Ethanol also depressed the contractions induced by exogenous noradrenaline. The resting membrane potentials recorded intracellularly from the smooth muscle cells were not affected by the alcohol. The excitatory junction potentials (EJPs) evoked by nerve stimulation decreased in amplitude, but the facilitation phenomena observed with repetitive stimulation remained unaltered. Ethanol slightly increased the frequency of the spontaneous EJPs, but decreased their amplitude. The extracellularly recorded action potentials from the small sympathetic nerve bundles innervating the vas deferens were suppressed by high concentrations of ethanol (more than 200 mM). These results indicate that ethanol inhibits adrenergic neuromuscular transmission in the vas deferens probably through depressing the sensitivity of the postsynaptic membrane to the transmitter and a block of axonal conduction in the presynaptic nerve terminals.

Extracellular potassium activity during frequency-dependent conduction block of giant axons in the metathoracic ganglion of the cockroach

In the metathoracic ganglion (T 3) of the cockroach, extracellular potassium activity (aK) was measured with ion-sensitive microelectrodes and intracellular recordings were simultaneously made from giant axons (GAs) during high frequency stimulation of the connectives. Blockade of spike conduction through T 3 was associated with intraganglionic aK rises of 0.2–0.5 mM, which were only 10% of the periaxonal aK rises suggested from GA depolarizations. When aK in the bath was increased 10-fold, GA conduction block during 1 Hz stimulation did not occur until much higher levels of aK and GA depolarization were achieved. The results suggest that glial sheaths surrounding GAs significantly impede K + movement, and may thus prevent non-specific axonal interactions, and that stimulus-induced conduction block is not primarily due to K +-induced depolarization and consequent Na +-inactivation.

N-hexane-induced changes in visual evoked potentials and electroretinograms of industrial workers

Visual evoked potentials (VEPs) and averaged extraocular electroretinograms (ERGs) were recorded from 15 workers occupationally exposed to n-hexane for 5–21 years and from 10 healthy control persons. The amplitude of the VEP components was clearly smaller among the exposed subjects with the exception of N0, which tended to be larger. In addition, the latencies of P1 and N1 were longer among the exposed workers, while that of P2 was slightly shorter. The peak-to-peak amplitude of the ERGs was also diminished among the exposed subjects. The changes were interpreted to indicate cerebral dysfunction, probably conduction block in intracerebral axons. n-Hexane is an aliphatic hydrocarbon found in gasoline and used in various industrial applications. It has been shown to cause axonal neuropathy of the dying-back type in both experimental animals and humans. According to the present findings the central nervous system is also susceptible to the toxic effects of n-hexane.

Transmitter release: ruthenium red used to demonstrate a possible role of sialic acid containing substrates.

1. The possible function of sialic acid-containing substrates (SACS) in synaptic terminals of Aplysia was studied by intracellular injection of ruthenium red and of neuraminidase. 2. Ruthenium red, a dye known to have sialic acid as a molecular target, blocked transmission irreversibly in both cholinergic (buccal ganglion) and non-cholinergic (cerebral ganglion) synapses. 3. An intracellular site of action is likely because much less ruthenium red was necessary to block transmission when it was injected intracellularly than when it was presented by bath perfusion. 4. Ca2+ spikes recorded in the presence of tetrodotoxin or in Na+-free solution were not modified by ruthenium red or neuraminidase injections or perfusions. It is therefore improbable that these substances blocked transmission by blocking voltage-dependent Ca2+ influx. 5. Strong electrotonic depolarization of a pre-synaptic interneurone in the presence of 10(-4) M-tetrodotoxin caused a sustained post-synaptic response, which was abolished by ruthenium red. This result eliminates axonal conduction block as the principal mechanism of ruthenium red action. 6. Post-synaptic responses to ionophoretically applied acetylcholine (ACh) were not modified by bath perfusion of 2 x 10(-2) M-ruthenium red. 7. Biochemical analysis of pools of [3H]ACh was performed after injection of a precursor, [3H]acetate, into an identified interneurone. Ruthenium red appeared to increase significantly the 'free' (cytoplasmic) ACh pool without any change of 'bound' (vesicular) [3H]ACh-pool. 8. A model is proposed in which SACS act as intracellular Ca2+ receptors involved in transmitter release.

Long-Term Adaptations of Sabella Giant Axons Tohyposmotic Stress

ABSTRACT Sabella is a euryhaline osmoconformer which is killed by direct transfer to 50% sea water, but can adapt to this salinity with progressive dilution of the sea water. The giant axons were adapted to progressive dilution of the bathing medium (both in vivo and in vitro) and were able to function at hyposmotic dilutions (down to 50 %) sufficient to induce conduction block in unadapted axons. Hyposmotic adaptation of the giant axon involves a decrease in intracellular potassium concentration which tends to maintain a relatively constant resting potential during adaptation despite the reduction in external potassium concentration. There is no appreciable change in the intracellular sodium concentration, but the relative sodium permeability of the active membrane increases during hyposmotic adaptation. This increase partially compensates for the reduction in sodium gradient across the axon membrane, during dilution of the bathing media, by increasing the overshoot of the action potentials recorded in hyposmotically adapted axons.