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E F Stanley

Publications and source records attributed to E F Stanley.

53 records · Page 3Linked to original sources
PubMed1985

Effects of IDPN-induced axonal swellings on conduction in motor nerve fibers.

Paranodal demyelination produces a reduction of conduction velocity and conduction block. The relative proportions of these changes appear to vary among different demyelinating disorders. In this study we have examined the effects on conduction of paranodal demyelination produced by giant axonal swellings. The axonal swellings were induced in rats by administration of beta, beta'-iminodipropionitrile (IDPN). In this experimental model synchronous axonal swellings occur in the proximal region of virtually every alpha-motorneuron without evidence of segmental demyelination or fiber loss. Conduction across the motor neuron was evaluated by two methods: a monosynaptic reflex pathway and intracellular recording from single motor neurons. Increases in the delay across the central region of the monosynaptic reflex pathway began between 2 and 4 days after toxin administration. Intracellular studies confirmed that the slowing occurred across the proximal regions of the motor axons; more distal regions of the motor axons were unaffected. The substantial reduction in conduction velocity over the swollen segment occurs with only moderate evidence of conduction block, as assayed by a reduction in the H-reflex/M-response amplitude ratio. Parallel morphological studies showed that in the enlarged fibers the myelin terminal loops maintained contact with the axon but were displaced from the paranodal region into the internode. The appearance of this "passive" paranodal demyelination correlated closely with the increase in conduction delay. We suggest that the contact maintained by the displaced myelin terminal loops with the axolemma allows saltatory conduction to continue, and explains the paucity of conduction block in this model despite the prominent conduction slowing.

Animals↗
PubMed1984

The action of cholinergic agonists on the squid stellate ganglion giant synapse.

Although the giant synapse in the squid stellate ganglion has served as a model in the understanding of the ionic and electrical changes that occur during the release of transmitter from nerve terminals, little is known about the pharmacology of this synapse or the identity of its neurotransmitter. In the present study, the suggestion that acetylcholine (ACh) is the excitatory transmitter at this synapse was tested by exploring the actions of cholinergic agents on the pre- and postsynaptic giant axons and on the excitatory postsynaptic potential (EPSP). A novel arterial perfusion technique that circumvents the diffusion barrier from the bathing medium to the synapse has been used to demonstrate a depolarizing action of ACh and its agonist carbachol on the post- but not the presynaptic axon. The cholinergic receptors are distinct from receptors activated by amino acids, such as glutamate, have a reversal potential of about -48 mV, are anion-permeable, and desensitize without blocking the EPSP. It is concluded that these receptors are involved in an inhibitory input onto the postsynaptic giant axon and, therefore, that ACh is most probably not the transmitter at the squid giant synapse.

Acetylcholine↗
PubMed1983

Rapid degradation of "new" acetylcholine receptors at neuromuscular junctions.

Acetylcholine receptors at innervated neuromuscular junctions are very stable, with half-lives reported to be 6 to 13 days. Their turnover is described as a first-order process, implying a single population of receptors. In this study, two subpopulations of acetylcholine receptors at normally innervated junctions have been identified. One has a rapid turnover rate with a half-life of 18.7 hours, similar to that of extrajunctional receptors, and the other has a slow turnover rate with a half-life of 12.4 days. The rapidly turned over subpopulation represents approximately 20 percent of the total junctional receptors. This finding may account for the discrepancies in previous reports of turnover rates and may explain the rapid reversibility in vivo of agents that "irreversibly" block acetylcholine receptors. This finding also implies that the synthesis rate of junctional acetylcholine receptors may be higher than previous estimates. The rapidly turned-over subpopulation may represent receptors that were newly inserted into the neuromuscular junction and that were not yet stabilized by an influence of the motor nerve.

Animals↗
PubMed1983

Botulinum toxin blocks quantal but not non-quantal release of ACh at the neuromuscular junction.

Botulinum (BOT) toxin is known to block quantal acetylcholine (ACh) release at the neuromuscular junction but little is known about its effect on non-quantal ACh release. We have examined the effect of BOT on non-quantal ACh release directly using a variant of the electrophysiological technique described by Katz and Miledi. This method is based on the observation that non-quantally released ACh results in a small, continual depolarization of the postsynaptic membrane, after inhibition of cholinesterase. This depolarization can be revealed by suddenly blocking ACh receptors with a pulse of curare, resulting in an abrupt hyperpolarization, the amplitude of which is presumed to be proportional to the rate of non-quantal ACh release. BOT treatment resulted in a marked decrease in quantal ACh release as shown by miniature endplate potential (m.e.p.p.) frequencies (control 0.65 +/- 0.33 m.e.p.p.s/s; BOT 0.03 +/- 0.03 m.e.p.p.s/s). However, non-quantal ACh release measured by the curare induced hyperpolarization, was not significantly different in control and BOT treated diaphragms (control 1.01 +/- 0.09 mV: BOT 1.03 +/- 0.11 mV). Our results show that BOT does not block non-quantal ACh release at a time when it has a profound effect on spontaneous quantal ACh release. This suggests that quantal and non-quantal ACh release take place through different release mechanisms.

Acetylcholine↗
PubMed1983

Canine neuroaxonal dystrophy.

Canine neuroaxonal dystrophy, a newly recognized familial disorder in Rottweiler dogs, is characterized by progressive sensory ataxia. Two of four dogs studied clinically were autopsied and the cerebellum was mildly atrophic. Massive numbers of axonal spheroids were present in many regions of the neuraxis but were most prominent in the dorsal horn of the spinal cord and the nuclei gracilis and cuneatus. Ultrastructurally, spheroids appeared to be swellings of distal axons which were filled with accumulations of smooth membrane-bound vesicles, membranous lamellae, dense bodies, and other organelles. Neuropathological changes were similar to those identified in human neuroaxonal dystrophy.

Animals↗
PubMed1980

Mechanisms of acetylcholine receptor loss in myasthenia gravis.

The fundamental abnormality affecting the neuromuscular junctions of myasthenic patients is a reduction of available AChRs, due to an autoimmune attack directed against the receptors. Antibodies to AChR are present in most patients, and there is evidence that they have a predominant pathogenic role in the disease, aided by complement. The mechanism of antibody action involves acceleration of the rate of degradation of AChRs, attributable to cross-linking of the receptors. In addition, antibodies may block AChRs, and may participate in producing destructive changes, perhaps in conjunction with complement. The possibility that cell-mediated mechanisms may play a role in the autoimmune responses of some myasthenic patients remains to be explored. Although the target of the autoimmune attack in myasthenic patients is probably always the acetylcholine receptors, it is not yet clear which of these immune mechanisms are most important. It is likely that the relative role of each mechanism varies from patient to patient. One of the goals of future research will be to identify the relative importance of each of these mechanisms in the individual patient, and to tailor specific immunotherapeutic measures to the abnormalities found.

Acetylcholine↗
PubMed1978

Effect of myasthenic immunoglobulin on acetylcholine receptors of intact mammalian neuromuscular junctions.

Degradation of acetylcholine receptors of intact mouse neuromuscular junctions was determined in vivo and in vitro by the release of radioactivity from mouse diaphragms labeled with 125I-alpha-bungarotoxin. Treatment of mice with immunoglobulin from myasthenic patients accelerated the degradation rate to approximately three times normal, in both intact animals and organ cultures. The released radioactivity was in the form of [125I]tyrosine, confirming the nature of the degradative process. Accelerated degradation of acetylcholine receptors at neuromuscular junctions may represent an important antibody-mediated mechanisms in myasthenia gravis.

Animals↗
PubMed1978

Reflexes evoked in human thenar muscles during voluntary activity and their conduction pathways.

Responses evoked by an electrical stimulus to the median nerve in a small muscle of the human hand during a voluntary contraction have been examined. Two of these responses have been shown to be evoked through reflex pathways. The first, with a mean afferent conduction velocity of 64 m/s and estimated central delay of about 0.8 ms, is identified as an H reflex. The second response, which has an undefined central pathway, has a mean afferent conduction velocity of 43 m/s and an estimated central delay of about 17 ms.

Adult↗