Nerve stimulation

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

The dB/d/is limited to 6 T/s out of concern that larger values could cause nerve stimulation. The r-f exposure is limited to a specific absorption rate (SAR) of 0.4 W/kg for the whole body, 0.32 W/kg averaged over the head, and less than 8.0 W/kg spatial peakia any one gram of tissue. These numbers are designed to limit the temperature rise to less than 1°C and localized temperature of no greater than 38°C head, 39°C tmnk, and 40°C ia the extremities. 

Contraction of muscle follows an increase of Ca " in the muscle cell as a result of nerve stimulation. This initiates processes which cause the proteins myosin and actin to be drawn together making the cell shorter and thicker. The return of the Ca " to its storage site, the sarcoplasmic reticulum, by an active pump mechanism allows the contracted muscle to relax (27). Calcium ion, also a factor in the release of acetylcholine on stimulation of nerve cells, influences the permeabiUty of cell membranes activates enzymes, such as adenosine triphosphatase (ATPase), Hpase, and some proteolytic enzymes and facihtates intestinal absorption of vitamin B 2 [68-19-9] (28). 

Local anesthetics produce anesthesia by blocking nerve impulse conduction in sensory, as well as motor nerve, fibers. Nerve impulses are initiated by membrane depolarization, effected by the opening of a sodium ion channel and an influx of sodium ions. Local anesthetics act by inhibiting the channel s opening they bind to a receptor located in the channel s interior. The degree of blockage on an isolated nerve depends not only on the amount of dmg, but also on the rate of nerve stimulation (153—156). 

NPY is primarily (but not exclusively) synthesised and released by neurons, which in the peripheral nervous system are predominantly sympathetic neurons [1]. In most cases, NPY acts as a co-transmitter that is preferentially released upon high frequency nerve stimulation. NPY can be metabolised by the enzyme dipeptidylpeptidase IV (also known as CD26) to generate the biologically active fragment NPY3 36. 

Nonadrenergic noncholinergic inhibitory responses to autonomic nerve stimulation are mainly mediated through NO synthesized by nNOS NO plays a crucial role as a neurotransmitter from the peripheral efferent nerves, thus being called nitrergic. This provides a... 

Glycogenolysis increases in muscle several hundred-fold immediately after the onset of contraction. This involves the rapid activation of phosphorylase by activation of phosphorylase kinase by Ca +, the same signal as that which initiates contraction in response to nerve stimulation. Muscle phosphorylase kinase has four... 

Peptides in the a-conotoxin family are inhibitors of nicotinic acetylcholine receptors. They were first isolated from C. geographus venom as components which cause paralysis in mice and fish when injected intraperitoneally (27). Early physiological experiments (28) indicated that a-conotoxins GI, GII, and GIA (see Table III) all act at the muscle end plate region. Mini end-plate potentials and end plate potentials evoked in response to nerve stimulation are inhibited in the presence of a-conotoxins in the nM to pM range. a-Conotoxin GI was subsequently shown to compete with rf-tubocurarine and a-bungarotoxin for the acetylcholine receptor (29). 

Figure 1.9 Comparison of the effects of an endogenously released and exogenously applied neurotransmitter on neuronal activity (identity of action). Recordings are made either of neuronal firing (extracellularly, A) or of membrane potential (intracellularly, B). The proposed transmitter is applied by iontophoresis, although in a brain slice preparation it can be added to the bathing medium. In this instance the applied neurotransmitter produces an inhibition, like that of nerve stimulation, as monitored by both recordings and both are affected similarly by the antagonist. The applied neurotransmitter thus behaves like and is probably identical to that released from the nerve...

While this chapter is concerned primarily with the neurochemical mechanisms which bring about and control impulse-evoked release of neurotransmitter, some of the methods used to measure transmitter release are described first. This is because important findings have emerged from studies of the effects of nerve stimulation on gross changes in transmitter release and intraneuronal stores. The actual processes that link neuronal excitation and release of transmitter from nerve terminals have been studied only relatively recently. The neurochemical basis of this stimulus-secretion coupling, which is still not fully understood, is described next. The final sections will deal with evidence that, under certain conditions, appreciable amounts of transmitter can be released through Ca +-independent mechanisms which do not depend on neuronal activation. 

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... 

Generally the concentration of DA remains remarkably constant irrespective of the level of neuronal activity. One reason for this is that nerve stimulation increases tyrosine hydroxylase activity and DA synthesis. It is thought that tyrosine hydroxylase can exist in two forms with low and high affinities for its tetrahydropteredine co-factor (BEI-4) and that nerve traffic increases the high-affinity fraction. 

While the amount of noradrenaline released from the terminals can be increased by nerve stimulation, it can be increased much more by drugs, like phenoxybenzamine, which block presynaptic a-adrenoceptors. These receptors are normally activated by increased noradrenaline in the synapse and trigger a feedback cascade, mediated by... 

Vagus nerve stimulation (VNS) may be used for adult patients with treatment-resistant depression. A pulse generator is surgically implanted under the skin of the left chest, and an electrical lead connects the generator to the left vagus nerve. Stimulation of this nerve sends signals to the brain. This therapy is intended to be used along with traditional therapies, such as pharmacotherapy and ECT.20... 

I exercise, and following a low-fat vegetarian diet all have been shown to reduce the intensity of the dysmenorrhea.17,28 Dietary changes also may shorten the duration of dysmenorrhea. These interventions require little time and minimal cost and are associated with little risk. Other nonpharmacologic options that may be considered before or, in most cases, after a trial of pharmacologic interventions include the use of transcutaneous electric nerve stimulation (TENS), acupressure, and acupuncture.17... 

J. N. Langley maintained an interest in the action of plant alkaloids throughout his fife. Through his work with nicotine (which can contract skeletal muscle) and curare (which abolishes this action of nicotine and also blocks the response of the muscle to nerve stimulation, as first shown by Claude Bernard), he was able to infer in 1905 that the muscle must possess a receptive substance ... 

Since in the normal state both nicotine and curari abolish the effect of nerve stimulation, but do not prevent contraction from being obtained by direct stimulation of the muscle or by a further adequate injection of nicotine, it may be inferred that neither the poison nor the nervous impulse acts directly on the contractile substance of the muscle but on some accessory substance. 

Describe the factors that influence the strength of skeletal muscle contraction including multiple motor unit summation, asynchronous motor unit summation, frequency of nerve stimulation, length-tension relationship, and diameter of the muscle fiber... 

Aghajanian, G.K., Wang, R.Y., and Baraban, J., Serotonergic and non-serotonergic neurons of the dorsal raphe reciprocal changes in firing induced by peripheral nerve stimulation, Brain Res. 153(1), 169-175, 1978. 

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