Synapses 371

Synapses are the contact points of two nerve cells or of a nerve cell with an effector cell (such as a muscle, glandular or sensory cell). It is at the synapse, exactly at the synaptic cleft, where the transfer of information from one cell to the next takes place. It is estimated that the diameter of a synaptic cleft, Le. the distance between the presynaptic membrane (part of the first cell) and the postsvnaptic membrane (part of the second cell), is about 100 300 pm. Depending on the carrier of information, electrical and chemical synapses can be distinguished  

The Electrical Part of the Cross-talk between Neurons 

Once the electrical signal has arrived at a chemical synapse (see Fig 4.2) a cascade of events is triggered with the arrival of an electrical impulse (an action potential), a chemical compound known as a neurotransmitter is released from the presynaptic side into the synaptic cleft. The released neurotransmitter then reaches the membrane of the second cell (postsynaptic membrane) where it interacts with a macromolecule, a so-called receptor. It is this neurotransmitter receptor interaction that triggers another cascade of (chemical) reactions within the second cell and this ultimately leads to the generation of an electrical signal within this cell. This signal then is transferred along this second cell s axon towards another synapse. 

Once a neurotransmitter is bound to the postsynaptieally located receptor a change in the electrical potential of the postsynaptic membrane occurs. Depending on both the type of transmitter and the properties of the postsynaptic receptor involved, the membrane potential of the second cell is 

The synapse is the region where signal coupling between, for example, two neurons takes place. In the synapse, the signal may pass, may he blocked, or may be modified. In the animal world, there are two types the chemical and the electrical synapse. 

In the electrical synapse, the distance between the cell membranes are just a few nanometers and much shorter than in the chemical synapse. The joining membranes open a direct channel between the intracellular compartments in the form of small tubules gap junctions), allowing direct ionic flow. Gap junctions are found in file visceral smooth muscles and in the cardiac muscle. Gap junctions allow direct signal transmission in both directions between neighboring muscle cells so that each cell does not need a direct innervation. 

Target tissues are often the other neurons. The action potential arrives along an axon, which spfits up in several synapses. These act as presynaptic terminals on other neurons. Oflier target tissue types are muscles, where a part of the muscle called a muscle group is innervated. Other targets are internal organs, blood vessels, intestines, and glands (eyes, sweat, saliva, tears, endocrine). 

Neuron excitation is dependent on the total information entering from all presynaptic terminals. Because there are thousands of inputs, no single input has any decisive influence. The inhibitory inputs have largest influence because there are much fewer inhibitory than excitatory presynaptic terminals. 

In the nerve system, there is summation—both spatial and temporal. This is easily illustrated with skin receptors. If a variahle skin contact area electrode is used for the examination of electric current perception, it is found that the current density threshold is dependent on die contact area. As the area is increased, the current density threshold is lower because of die summation effect of the receptor responses in the skin (Martinsen et al., 2004). Because of the temporal summation, the excitatory signals must be synchronized in order to trigger the neuron. However, slow changes of the presynaptic DC levels may also make a cell more or less excitable. Such level shifts are according to the Nernst concept and are also under hormonal control. 

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The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters, substances that carry messages across a synapse from one neuron to another Several of these neurotransmitters arise from l tyrosine by structural modification and decarboxylation as outlined m Figure 27 5... 

Thus nicotinoids that have the highest insecticidal action have the highest piC and, consequently, exist largely in the ionized form at physiological pH. This produces the anomaly that the compounds that are most highly ionized react most rapidly with the receptor protein, yet they are less able to penetrate through the ionic barrier surrounding the insect nerve synapse. 

Two specialties of the nervous system are speed and localization, accompHshed using highly developed electrical signaling and close cellular apposition. At specialized points of communication, such as the synapse and the neuromuscular junction, the cells are separated by a nanometer or less. 

D. J. Triggle and C. R. Triggle, Chemical Pharmacology of the Synapse, Academic Press, New York, 1977, Chapts. 2—3. 

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. 

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

Diethyl 0-(3-methyl-5-pyrazolyl) phosphate (722) and 0,0-diethyl 0-(3-methyl-5-pyrazolyl) phosphorothioate (723) were prepared in 1956 by Geigy and they act, as do all organophosphates in both insects and mammals, by irreversible inhibition of acetylcholinesterase in the cholinergic synapses. Interaction of acetylcholine with the postsyn-aptic receptor is therefore greatly potentiated. 0-Ethyl-5-n-propyl-0-(l-substituted pyrazol-4-yl)(thiono)thiolphosphoric acid esters have been patented as pesticides (82USP4315008). 

The human brain is comprised of many millions of interconnected units, known individually as biological neurons. Each neuron consists of a cell to which is attached several dendrites (inputs) and a single axon (output). The axon connects to many other neurons via connection points called synapses. A synapse produces a chemical reaction in response to an input. The biological neuron fires if the sum of the synaptic reactions is sufficiently large. The brain is a complex network of sensory and motor neurons that provide a human being with the capacity to remember, think, learn and reason. 

Picrotoxin, a potent antagonist of 7-aminobutyric acid at neural synapses, has been synthesized from (R)-(-) carvone as SM-goal (Sections 3.1 and 6.5). 

FIGURE 5.46 Interaction of the serine hydroxyl residue in the catalytically active site of acetylcholinesterase enzyme with esters of organophosphates or carbamates. The interaction leads to binding of the chemical with the enzyme, inhibition of the enzyme, inhibition of acetylcholine hydrolysis, and thus accumulation of acetylcholine in the synapses. 

Neurons have three parts the cell body and dendrites, the axon, and axon terminals. The cell body contains the nucleus and the organelles needed for metabolism, growth, and repair. The dendrites are branched extensions of the cell body membrane. The axon is a long, thin structure which transfers electrical impulses down to the terminals. The axon divides into numerous axon terminals and it is in this specialized region that neurotransmitters are released to transmit information from one neuron to its neighbors. The synapse has been defined as the space between two subsequent interrelated neurons. ... 

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. 

Adenosine production in the synapse is not through vesicular release in response to nerve firing, as is the case for classical neurotransmitters. Rather, adenosine acts as a local autacoid, the release of which increases upon stress to an organ or tissue. Most cells in culture and in situ produce and release adenosine extracellularly. This... 

Altered synaptic properties Numerous changes in the properties of inhibitory (GABAergic) and excitatory (glutamatergic) synapses have been reported. While the simple adage of an imbalance between inhibitory and excitatory neurotransmission in epilepsy is not generally applicable, some forms of inhibition are lost or impaired in epilepsy. Likewise, an increased function of glutamate receptors has been demonstrated in some brain areas. 

A receptor on nerve endings within a synapse that responds to the released neurotransmitter from that neuron. This then feeds back to the same neuron and negatively regulates the synthesis and release of that neurotransmitter. 

Long nerve-cell process transmitting the action potential and ending as the synapse. 

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