Endings, of nerves

The electricity-producing system of electric fishes is built as follows. A large number of flat cells (about 0.1 mm thick) are stacked like the flat unit cells connected in series in a battery. Each cell has two membranes facing each other. The membrane potentials of the two membranes compensate for each other. In a state of rest, no electrostatic potential difference can be noticed between the two sides of any cell or, consequently, between the ends of the stack. The ends of nerve cells come up to one of the membranes of each cell. When a nervous impulse is applied from outside, this membrane is excited, its membrane potential changes, and its permeability for ions also changes. Thus, the electrical symmetry of the cell is perturbed and a potential difference of about 0.1 V develops between the two sides. Since nervous impulses are applied simultaneously to one of the membranes in each cell, these small potential differences add up, and an appreciable voltage arises between the ends of the stack. 

By destroying the protein, the toxin prevents the release of the neurotransmitter acetylcholine from small packets at the ends of nerves by exocytosis. These nerves, attached to voluntary muscles, need acetylcholine to allow the flow of signals (impulses) between the nerve and the muscle. By preventing the release of acetylcholine, botulinum toxin blocks muscle contraction, causing paralysis and relaxation. The therapeutic action relies on relaxation of muscles, generally in the face. It is therefore used to treat blepharospasm (uncontrolled contractions) and stroke-induced permanent facial muscle contractions. 

How organophosphates are toxic to nerves. Acetylcholine is a neuro-transmitter chemical present in the ends of nerves. Acetylcholinesterase is an enzyme which breaks down acetylcholine so that it is no longer effective at causing muscle contraction. Organophosphates inhibit this enzyme allowing acetylcholine to accumulate. 

How botulinum toxin works. The toxin inhibits the release of the chemical acetylcholine, a neurotransmitter present in the ends of nerves. The nerve impulses are inhibited, so the muscles relax and the viaim is paralysed. For more detail see the explanatory box. 

A chemical released from the ends of nerves as a (neuro)transmitter when these are stimulated, acetylcholinesterase... 

The posterior pituitary gland, also known as the neurohypophysis, contains the endings of nerve axons arising from distinct populations of neurons in the supraoptic and paraventricular nuclei that synthesize either arginine vasopressin or oxytocin. Arginine vasopressin plays an important role in water homeostasis (see Chapter 29) oxytocin plays important roles in labor and parturition and in... 

Arvid Carlsson was working with Brodie at that time in research involving the neurotransmitter, 5-HT. Amines and peptides released from axons at the end of nerve terminals cross synapses and activate or inhibit the electrical activity of postsynaptic neurons by binding to receptor proteins on the postsynaptic neurons. It was found that DA, 5-HT, GABA, benzodiazepine, acetylcholine, opioid, epinephrine, and NE are bound by receptors. Epinephrine is part of a class of molecules known as catecholamines that regulate the activity of the sympathetic nervous system. 

Primary repair of nerves and tendons is not imdertaken at the initial debridement. Minimal debridement should be performed and the end of nerves marked with a suture. Bone ends are trimmed and dead... 

Miscellaneous organelles and particles. Many are known, but only those of possible interest in therapy will be mentioned here. Acetylcholine, synthesized in motor nerve terminals, is stored there in minute vesicles (Whittaker, 1963), which become ruptured when the arrival of a nervous impulse releases calcium ions. Synaptosomes which are much larger, are the snapped-off pre-synaptic ends of nerves, and can be isolated by centrifugation (Blaschko, 1959). Depending on their source, they may contain noradrenaline, dopamine, serotonin, the corticotrophic-releasing factor, and other transmitters, but never acetylcholine. Catecholinergic synaptosomes actually synthesize catecholamines (Patrick and Barchas, 1974). The rupture of presynaptic vesicles in the insect is thought to play an important part in the insecticidal action of DDT (see Section .6e). 

The same author found Z-hyoscine sixteen to eighteen times as active as the d-isomeride in antagonising the action of pilocarpine on the termination of nerves in the salivary glands, -while both isomerides are equally active on nerve ends in striated and unstriated muscle and on the central nervous system. 

P-Homochelidonine was examined by Meyer and von Engel, and the results, as quoted by Sehmidt, indicate that in frogs -homoehelidonine behaves like ehelidonine, and that in mammals it eauses slight nareosis and a transitory fall in blood pressme, followed by eonvulsions of the type indueed by camphor, slowing of the pulse and, in large doses, paralysis of the vaso-motor centres. It also paralyses the ends of the sensory nerves. ... 

Tree like networks of nerve fiber called dendrites protrude outward from the neuron s cell body, or soma. Extending outward from the soma is also a long fiber called the axon that itself eventually branches out into a set of strands and sub strands. At the ends of these strands are the transmitting ends of communication junctions between nerve fibers called synapses. The receiving ends of these junctions exist both on dendrites and on the somas themselves. Each neuron is typically connected to several thousand other neurons. 

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

N euro transmitters are chemical substances called neurohormones. These are released at Hie nerve ending that facilitate the transmission of nerve impulses. The two neurohormones (neurotransmitters) of the sympathetic nervous system are epinephrine and norepinephrine Epinephrine is secreted by the adrenal medulla Norepinephrine is secreted mainly at nerve ending of sympathetic (also called adrenergic) nerve fibers (Pig. 22-2). 

Myasthenia gravis is a disease tiiat involves rapid fatigue of skeletal muscles because of die lack of ACh released at die nerve endings of parasympathetic nerve fibers. Drugs used to treat this disorder include ambeno-nium (Mytelase) and pyridostigmine (Mestinon). 

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

Figure 2. Muscle stimulation, a) a single nerve impulse (stimulus) causes a single contraction (a twitch). There is a small delay following the stimulus before force rises called the latent period, b) A train of stimuli at a low frequency causes an unfused tetanus. Force increases after each progressive stimulus towards a maximum, as calcium levels in the myofibrillar space increase. But there is enough time between each stimulus for calcium to be partially taken back up into the sarcoplasmic reticulum allowing partial relaxation before the next stimulus occurs, c) A train of stimuli at a higher frequency causes a fused tetanus, and force is maximum. There is not enough time for force to relax between stimuli. In the contractions shown here, the ends of the muscle are held fixed the contractions are isometric.

The somatic motor nervous system or voluntary nervous system consists of nerve libers that irmervate skeletal muscle motor end-plates. 

A substance which is released at the end of a nerve fibre by the arrival of a nerve impulse and by diffusing across the synapse or junction effects the transfer of the impulse to another nerve fibre (or muscle fibre or some receptor). 

Many early studies of transmitter release depended on measuring its concentration in the effluent of a stimulated, perfused nerve/end-organ preparation. This technique is still widely used to study drug-induced changes in noradrenaline release from sympathetic neurons and the adrenal medulla. However, it is important to realise that the concentration of transmitter will represent only that proportion of transmitter which escapes into the perfusate ( overflow ) (Fig. 4.2). Monoamines, for instance, are rapidly sequestered by uptake into neuronal and non-neuronal tissue whereas other transmitters, such as acetylcholine, are metabolised extensively within the synapse. Because of these local clearance mechanisms, the amount of transmitter which overflows into the perfusate will depend not only on the frequency of nerve stimulation (i.e. release rate) but also on the dimensions of the synaptic cleft and the density of innervation. 

One approach, and the first to be adopted, is to study transmitter release from slices which have been preloaded with radiolabelled transmitter. In these experiments, drug-induced changes in the release of transmitter is usually monitored using the doublepulse technique. This involves comparing the effects of a test drug on the amount of transmitter released in response to a reference pulse and a second identical test pulse. If all the radiolabelled transmitter that overflows in the effluent is collected, and the amount which remains in the slice at the end of the experiment is also measured, it is possible to calculate not only how much radiolabelled transmitter was originally contained in the slice but also the effects of drugs on fractional release , i.e. the proportion of the store of radiolabelled transmitter which is released by nerve stimulation. As with... 

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