Nerve impulse transmission

O MS symptoms are a function of the position of lesions within the CNS. Because myelin increases the speed of nerve impulse transmission, demyelination slows the speed of transmission. No impulses can be transmitted if the axon is transected. The primary symptoms of MS are caused by this delay or cessation of impulses. Secondary symptoms of MS result from the primary symptoms. 

Toxins present a variety of both incapacitating and lethal effect. Most toxins of military significance can be broadly classified in one of two ways. Neurotoxins disrupt the nervous system and interfere with nerve impulse transmission similar to nerve agents (Chapter 1). However, all neurotoxins do not operate through the same mechanism of action or do they produce the same symptoms. Cytotoxins are poisons that destroy cells or impair cellular activities. Symptoms may resemble those of vesicants (Chapter 3) or they may resemble food poisoning or other diseases. Toxins may also produce effects that are a combination of these general categories. The consequences of intoxication from any individual toxin can vary widely with route of exposure and dose. In addition, some toxins act as biomediators and cause the body to release excessive, and therefore harmful, amounts of chemicals that are normally produced by the body. 

Perhaps the most prominent and well-studied class of synthetic poisons are so-called cholinesterase inhibitors. Cholinesterases are important enzymes that act on compounds involved in nerve impulse transmission - the neurotransmitters (see the later section on neurotoxicity for more details). A compound called acetylcholine is one such neurotransmitter, and its concentration at certain junctions in the nervous system, and between the nervous system and the muscles, is controlled by the enzyme acetylcholinesterase the enzyme causes its conversion, by hydrolysis, to inactive products. Any chemical that can interact with acetylcholinesterase and inhibit its enzymatic activity can cause the level of acetylcholine at these critical junctions to increase, and lead to excessive neurological stimulation at these cholinergic junctions. Typical early symptoms of cholinergic poisoning are bradycardia (slowing of heart rate), diarrhea, excessive urination, lacrimation, and salivation (all symptoms of an effect on the parasympathetic nervous system). When overstimulation occurs at the so-called neuromuscular junctions the results are tremors and, at sufficiently high doses, paralysis and death. 

Acetylcholine is a relatively small molecule that is responsible for nerve-impulse transmission in animals. As soon as it has interacted with its receptor and triggered the nerve response, it must be degraded and released before any further interaction at the receptor is possible. Degradation is achieved by hydrolysis to acetate and choline by the action of the enzyme acetylcholinesterase, which is located in the synaptic cleft. Acetylcholinesterase is a serine esterase that has a mechanism similar to that of chymotrypsin (see Box 13.5). 

Mechanism of Action A benzodiazepine that depresses all levels of the CNS inhibits nerve impulse transmission in the motor cortex and suppresses abnormal discharge in petit mal seizures. Therapeutic Effect Produces anxiolytic and anticonvulsant effects. 

Mechanism of Action An herb that produces genital blood vessel dilation, improves nerve impulse transmission to genital area. Increases penile blood flow, central sympathetic excitation impulses to genital tissues. Therapeutic Effect Improves sexual vigor, affects impotence. 

Ion transport is central to nerve impulse transmission both along the axon and at the synapse and many neurotoxicants elicit effects by interfering with the normal transport of these ions (Figure 11.6). The action potential of an axon is maintained by the high concentration of sodium on the outside of the cell as compared to the low concentration inside. Active transporters of sodium (Na+K+ ATPases) that actively transport sodium out of the cell establish this action potential. One action of the insecticide DDT resulting in its acute toxicity is the inhibition of these Na+K+ ATPases resulting in the inability of the nerve to establish an action potential. Pyrethroid insecticides also elicit neurotoxicity through this mechanism. DDT also inhibits Ca2+Mg2+ ATPases, which are important to neuronal repolarization and the cessation of impulse transmission across synapses. 

Figure 11.6 Ion channels that facilitate nerve impulse transmission and that are susceptible to perturbation by various toxicants and drugs. Ion transport inhibitors are indicated in parentheses.

Alan L. Hodgkin (1914—1998) and Andrew F. Huxley (1917- ), both English physiologists, first work out the mechanism of nerve-impulse transmission, showing that a sodium pump system works to carry impulses. 

John Carew Eccles (1903-1997), Australian neurophysiologist, shares a Nobel Prize for his work on the mechanisms of nerve-impulse transmission. He also suggests that the mind is separate from the brain. The mind, he affirms, acts upon the brain by effecting subtle changes in the chemical signals that flow among brain cells. 

There is not space here to explain the process of nerve impulse transmission. It is an electrical process and involves pumping of Na+ and K+ ions across barriers. It should be noted that there are cells other than neurons in the nervous system, of which the most abundant are glial cells. 

The alkaline earth metals (group 2A of the periodic table) include Mg and Ca, which play both structural and physiological roles. Aside from its structural importance in bones and teeth, calcium is critical in processes ranging from vascular tone, nerve impulse transmission, muscle contraction, blood clot formation, the secretion of hormones such as insulin, and cell signaling. Calcium levels in cells, blood, and extracellular fluid are very tightly controlled. If calcium intake is insufficient, calcium is liberated from bones in order to support these physiological functions. 

Figure 4.10. Overview of nerve impulse transmission in chemical synapses. The action potential in the presynaptic nerve cell induces release of the nemotransmitter (e.g., acetylcholine) into the synaptic cleft. The transmitter binds to its receptor, e.g. the nicotinic acetylcholine receptor (NAR). The NAR is a hgand-gated channel it will open and become permeable to both and Na. This will move the membrane potential toward the average of the two respective equilibrium potentials however, in the process, the firing level of adjacent voltage-gated sodium charmels will be exceeded, and a full action potential will be triggered (inset).

Lithium, sodium, and potassium, and their compounds, are of considerable biochemical and industrial importance. " Lithium salts can control manic-depressive psychoses, the Na+/K+ concentration ratio is crucial to nerve impulse transmission, and potassium formulations dominate the plant fertilizer market. Lithium and its salts are used in the production of high-strength and low-density alloys, of lubricating... 

Sarin was involved in terrorist attacks in Japan (Okumura et al, 2003 Okudera, 2002). The increase in sympathetic and parasympathetic tone results in tachycardia, ST-segment modulation (Abraham et al, 2001), and arrhythmia. Inhibition of cholinesterase within the neuroeffector junction also affects nerve impulse transmission by direct action. Direct action on muscarinic or nicotinic ACh receptors (Somani et al, 1992) is observed when the blood level of sarin exceeds the micromolar level. Sarin inhibits RBC-AChE 80-100% as well as plasma-BChE between 30 and 50% (Grob and Harvey, 1958). It also binds to aliesterase, an enzyme that contributes to ester-link hydrolysis. 

Calcium is an electrolyte in extracellular fluid and intracellular fluid and assists in nerve impulse transmission, blood clotting, muscle contraction, and formation of teeth and bone. Calcium combines with phosphate in bone and albumin in serum. 

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