The Nerve Impulse

Choline functions in fat metaboHsm and transmethylation reactions. Acetylcholine functions as a neurotransmitter in certain portions of the nervous system. Acetylcholine is released by a stimulated nerve cell into the synapse and binds to the receptor site on the next nerve cell, causing propagation of the nerve impulse. 

Rgure 22-2. Neurotransmission in the central nervous system. Neurotransmitter molecules (eg, norepinephrine), released by the presynaptic nerve, cross the synapse and bind with receptors in the cell membrane of the postsynaptic nerve, resulting in the transmission of the nerve impulse. 

After receiving lidocaine hydrochloride (Xylocaine HCI), the threshold is raised to a higher level, allowing fewer stimuli to reach the threshold. This results in decreased stimulation of the nerve fiber and prevents conduction of the nerve impulses causing the arrthvthmia. 

The AChR is composed of five subunits, ql2Pi - A neurotoxin attaches to the a subunit. Since there are 2 mol of the a subunits, 2 mol of neurotoxins attach to 1 mol of AChR. A neurotransmitter, acetylcholine (ACh), also attaches to the a subunit. When the ACh attaches to the AChR, the AChR changes conformation, opening up the transmembrane pore so that cations (Na" ", K ) can pass through. By this mechanism the depolarization wave from a nerve is now conveyed to a muscle. The difference between neurotoxin and ACh is that the former s attachment does not open the transmembrane pore. As a consequence, the nerve impulse from a nerve cannot be transmitted through the postsynaptic site (27). 

Saltatory conduction results in a significant increase in the velocity of conduction of the nerve impulse down the axon compared to that of local current flow in an unmyelinated axon (see Table 4.2). The speed of conduction is... 

Davenport, H. W. Early history of the concept of chemical transmission of the nerve impulse. Physiologist 34 129-190, 1991. 

Neuromuscular transmission (B) of motor nerve impulses to the striated muscle fiber takes place at the motor endplate. The nerve impulse liberates acetylcholine (ACh) from the axon terminal. ACh binds to nicotinic cholinocep-tors at the motor endplate. Activation of these receptors causes depolarization of the endplate, from which a propagated action potential (AP) is elicited in the surrounding sarcolemma. The AP triggers a release of Ca from its storage organelles, the sarcoplasmic reticulum (SR), within the muscle fiber the rise in Ca concentration induces a contraction of the myofilaments (electromechanical coupling). Meanwhile, ACh is hydrolyzed by acetylcholinesterase (p. 100) excitation of the endplate subsides. if no AP follows, Ca + is taken up again by the SR and the myofilaments relax. 

Alkali and alkaline-earth cations (AC and AEC) occupy an important position in matter and in life. In biology, they are present as charge carriers in ionic processes (cf. the role of Na+ and K+ in the propagation of the nerve impulse) and as structure holders (Mg2+, Ca2+). 

Tubocurarine acts as a competitive inhibitor in the nicotinic acetylcholine receptor, meaning that the nerve impulse is blocked by this alkaloid. Tubocurarine is used in surgical practice as a muscle relaxant. These alkaloids have an observably large spectrum of activity and possible applications. Their utilization in the development of new applications is therefore relatively active in modern medicine. 

The basic features of the signaling system found in different cells are remarkably similar. It appears that protein phosphorylation is a hnal common pathway in the molecular mechanisms through which neurotrans-mitters, hormones, and the nerve impulse produce many of their biological effects in target cells. 

Procaine and the other local anaesthetic drugs prevent the generation and the conduction of the nerve impulses. Their main site of action is the cell membrane, since conduction block can be demonstrated in giant axons from which the axoplasm has been removed [25]. 

Local anaesthetics block both the generation and conduction of the nerve impulse. 

At the end of an axon, where it meets another nerve cell or an effector cell (a cell such as a muscle or a gland cell), there is a gap or junction that is usually about 10 to 20 nm wide and this is known as a synapse. The passage of the nerve impulse across this synapse is chemical rather than electrical. When the nerve impulse reaches a synapse it causes the release of a chemical transmitter that is usually acetylcholine. Other transmitters have been identified and these include L-glutamate and y-aminobutyric acid (GABA). The released acetylcholine interacts with a receptor on the... 

Arrival of the nerve impulse at a nerve terminal leads to the opening of voltage-gated Ca2+ channels and rapid influx of Ca2+. The increase in Ca2+ concentration at the active zone from a basal level of 100 nM to more than 200 pM results in an appropriate neurotransmitter release within 200 ps (Barrett and Stevens, 1972 Linas et al., 1981 1992 Augustine and Neher, 1992 Zucker, 1993 Heidelberger et al., 1994). 

The axon is effectively insulated from the surrounding medium by the myelin sheets except for special regions, the nodes of Ranvier, which lie at 1-to 2-mm intervals along the nerve. The nerve impulse in effect jumps from one nerve to the next. This saltatory conduction occurs much more rapidly (up to 100 m / s) than conduction in unmyelinated axons. It depends upon Na+ and K+ channels that are concentrated in the nodes of Ranvier. 

The primary photochemical process of vision is therefore the cis-trans isomerization of retinal in rhodopsin. The free protein opsin then leads to the production of the nerve impulse through a secondary biochemical process... 

The exact point at which the nerve impulse is transmitted is not established with certainty, but it has to occur before the hydrolysis step because hydrolysis is too slow to account for the nerve impulse. One theory suggests that an electrical signal is generated at the instant of light absorption by electron transfer to a w------> rr singlet excited state that has substantially charged carbon atoms. 

The message of calcium is conveyed from the troponin to which it binds, via tropomyosin to the actin filament193-198).As soon as the nerve impulse ceases, the calcium becomes quickly removed and returned to the storage sites situated in the membranes of the sarcoplasmic reticulum. When Ca2+ concentration in the sarcoplasm reaches 1 x 10-7 molar, the fiber is relaxed. 

Agents which block responses of effector cells to sympatho-adrenal stimuli may be termed adrenergic blocking agents. It is only at these effector cells that adrenergic mediators are involved in transmission of the nerve impulse. For a number of reasons, the frequently used terms adrenolytic and sympatholytic agents are ambiguous and undesirable (see 70). 

Acetylcholine is a neurotransmitter that functions in conveying nerve impulses across synaptic clefts within the central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across the synapse by the release of acetylcholine, acetylcholinesterase is released into the synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of the nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation. Organophosphorus and carbamate pesticides (Chapter 5) along with some nerve gases (i.e., sarin) elicit toxicity via this mechanism. 

One of the most important hydrolases is acetylcholine esterase (cholinesterase). Acetylcholine is a potent neurotransmitter for voluntary muscle. Nerve impulses travel along neurons to the synaptic cleft, where acetylcholine stored in vesicles is released, carrying the impulse across the synapse to the postsynaptic neuron and propagating the nerve impulse. After the nerve impulse moves on, the action of the neurotransmitter molecules must be stopped by cholinesterase, which hydrolyzes acetylcholine to choline and acetic acid. Some dangerous toxins such as the exotoxin of Clostridium botulinum and saxitoxin interfere with cholinesterase, and many nerve agents such as tabun and sarin act by blocking the hydrolytic action of cholinesterase, see also Enzymes Hydrolysis. 

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