Nerve action

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne... 

Lowenstein (27) found an approximate correlation between the nerve action potential produced by 1.6% pyrethrins applied externally and 0.3% pyrethrins applied directly to the nerve cord. 

All transmitters (except NO) are released by the following cascade arrival of the nerve action potential at the terminal - opening of voltage-sensitive Ca2+... 

Action potentials, self-propagating. Action potentials of smooth muscle differ from the typical nerve action potential in at least three ways. First, the depolarization phases of nearly all smooth muscle action potentials are due to an increase in calcium rather than sodium conductance. Consequently, the rates of rise of smooth action potentials are slow, and the durations are long relative to most neural action potentials. Second, smooth muscle action potentials arise from membrane that is autonomously active and tonically modulated by autonomic neurotransmitters. Therefore, conduction velocities and action potential shapes are labile. Finally, smooth muscle action potentials spread along bundles of myocytes which are interconnected in three dimensions. Therefore the actual spatial patterns of spreading of the action potential vary. 

Veratridine is a complex lipophilic alkaloid that also binds to sodium channels, causing them to stay open and thereby disrupting the transmission of nerve action potential. It is found in the seeds of a member of the Liliaceae, Schoenocaulon... 

Pyrethroids, such as p,p -DDT, are toxic because they interact with Na+ channels of the axonal membrane, thereby disturbing the transmission of nerve action potential (Eldefrawi and Eldefrawi 1990, and Chapter 5, Section 5.2.4 of this book). In both cases, marked hydrophobicity leads to bioconcentration of the insecticides in the axonal membrane and reversible association with the Na+ channel. Consequently, both DDT and pyrethroids show negative temperature coefficients in arthropods increasing temperature brings decreasing toxicity because it favors desorption of insecticide from the site of action. 

The effects of neurotoxic chemicals upon nerve action potential have been measured both in vertebrates and insects. Of particular interest has been the comparison... 

The effects of DDT on nerve action potential are illustrated in Figure 16.1. In nerves poisoned by the insecticide, there is a prolongation of the sodium current and a consequent delay in returning to the resting potential. This can result in the... 

Disturbance of nerve action Persistent insecticides potential... 

There is ample precedent for a modulatory role of K channels in behavior. The K channel blocker, 4-AP, selectively blocks component T (Bartschat and Blaustein 1985a). prolongs nerve action potentials, and enhances neurotransmitter release (Llinas et al. 1975). In man, intoxication with this agent may lead to dissociative behavior, agitation, confusion, convulsions, and coma (Spyker et al. 1980). However, the behavioral aberrations induced by 4-AP differ qualitatively from those induced by PCP. This implies that block of various types of presynaptic K channels may modify behavior and mental activity however, the precise nature of the behavioral manifestations is likely to depend upon the specific type of K channel that is affected. 

A decrease in the amplitude of the sensory nerve action potential has also been observed in a group of 20 asymptomatic workers exposed to -hexanc (Pastore et al. 1994). The subjects of this study were selected on the basis of urinary levels of the n-hexane metabolite 2,5-hexanedione (See Sections 2.3 and 2.7) exceeding 5 mg/L and compared to a group of unexposed laboratory workers. Mean years worked was 8.13 (range, 1.5—23 years). Sensory and motor nerve conduction velocities and distal latencies were normal in all nerves tested. However, significant decreases were found in sensory nerve action potential amplitude in the median, sural, and ulnar nerves. Neither the level of 2,5-hexanedione in urine nor age correlated with the changes in amplitude however, there was a significant correlation between years worked and amplitude. 

The basic information regarding nerve physiology is fundamental to all possible applications, but the moment one becomes interested in applications, that is, doing anything about anyone s nerve action, biochemical individuality becomes a potent factor. If unrecognized, it is an enemy if recognized and taken into account, it may be a powerful ally. 

In the central nervous system, symptoms observed in animals following exposure include tremors, convulsions, ataxia, and changes in EEG patterns (Formanek et al. 1976). These central nervous system symptoms could be due either to (1) inhibition of the Na /K ATPase or the Ca /Mg ATPase activity, which can then interfere with nerve action or release of neurotransmitters (Yamaguchi et al. 

Electroneutrality, nerve action activation, osmotic pressure control, maintain ionic strength outside cell (as NaCl), maintain cell potential... 

To summarize there are two learning paradigms in the context of a reflex action controlled by a single ganglion in an experimental animal in which electrical measurements of nerve action are relatively easy. This experimental system permitted Kandel to map the neural circuit responsible for the gill-withdrawal reflex. The neural... 

Heptachlor epoxide is more toxic then heptachlor. The acute oral LD50 for heptachlor epoxide in rodents and rabbits ranged from 39 to 144mg/kg3 After dietary exposure of rats, heptachlor epoxide caused hepatic cell vacuolization at all dose levels (0.5-10 ppm for up to 108 weeks). Degeneration, hepatomegaly, and regeneration were also reported. Like heptachlor, the ability of heptachlor epoxide to induce lethality after acute exposure may involve its ability to interfere with nerve action or release of neurotransmitters and to inhibit the function of the receptor for y-aminobutyric acid. ... 

Neuromuscular transmission involves the events leading from the liberation of acetylcholine (ACh) at the motor nerve terminal to the generation of end plate currents (EPCs) at the postjunctional site. Release of ACh is initiated by membrane depolarization and influx of Ca++ at the nerve terminal (Fig. 28.1). This leads to a complex process involving docking and fusion of synaptic vesicles with active sites at the presynaptic membrane. Because ACh is released by exocytosis, functional transmitter release takes place in a quantal fashion. Each quantum corresponds to the contents of one synaptic vesicle (about 10,000 ACh molecules), and about 200 quanta are released with each nerve action potential. 

The aminopyridines (4-aminopyridine 3,4-diaminopyri-dine) accelerate spontaneous exocytosis at central and peripheral synapses. There is also an increase in the number of transmitter quanta released by a nerve action potential. This is probably the result of increased Ca++ inflow at the terminals due to a reduction of K+ conductance and prolongation of the nerve action potential. Muscle strength is increased in patients with the Lambert-Eaton myasthenic syndrome and in others poisoned with botuUnum E toxin (discussed later). Improvement in uncontrolled spasms, muscle tone, and pulmonary function is noted in patients with multiple sclerosis or long-standing spinal cord damage. Side effects that limit clinical utility include convulsions, restlessness, insomnia, and elevated blood pressure. Of the two agents, 3,4-diaminopyridine is the more potent and crosses the blood-brain barrier less readily. 

Guanidine hydrochloride is the drug of choice in the management of patients with myasthenic syndrome and may be of use in the treatment ofbotulinum intoxication. Its ability to enhance transmitter release may involve a block of K+ channels and prolongation of the nerve action potential. 

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