Nerve synapse

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. 

Neurohumoral transmitters are chemicals that facilitate the transmission of nerve impulses across nerve synapses and neuroeffector junctions. Acetylcholine is a neurohumoral transmitter that is present in the peripheral autonomic nervous system, in the somatic motor nervous system, and in some portions of the central nervous system. 

Ionic Solution Theory, H. L. Friedman, Wiley, New York, 1953, is a standard work in the held, but is a bit mathematical and can be difficult to follow. An easier book to follow is Ions, Electrodes and Membranes (second edition) by Jin Koryta, Wiley, Chichester, 1992, and is an altogether more readable introduction to the topic. It can also be trusted with details of pH electrodes and cells. Its examples are well chosen, many being biological, such as nerves, synapses, and cell membranes. It is probably the only book of its kind to contain cartoons. 

Inhibition of the two principal human cholinesterases, acetylcholinesterase and pseudocholinesterase, may not always result in visible neurological effects (Sundlof et al. 1984). Acetylcholinesterase, also referred to as true cholinesterase, red blood cell cholinesterase, or erythrocyte cholinesterase is found in erythrocytes, lymphocytes, and at nerve synapses (Goldfrank et al. 1990). Inhibition of erythrocyte or lymphocyte acetylcholinesterase is theoretically a reflection of the degree of synaptic cholinesterase inhibition in nervous tissue, and therefore a more accurate indicator than pseudocholinesterase activity of inhibited nervous tissue acetylcholinesterase (Fitzgerald and Costa 1993 Sundlof et al. 1984). Pseudocholinesterase (also referred to as cholinesterase, butyrylcholinesterase, serum cholinesterase, or plasma cholinesterase) is found in the plasma, serum, pancreas, brain, and liver and is an indicator of exposure to a cholinesterase inhibitor. 

Exposure to disulfoton can result in inhibition of acetylcholinesterase activity, with consequent accumulation of acetylcholine at nerve synapses and ganglia leading to central nervous system, nicotinic, and muscarinic effects (see Section 2.2.1.4 for more extensive discussion). 

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

The neurotransmitter at the sensory nerve-motor nerve synapse proved to be glutamate (incidentally, also the major excitatory neurotransmitter in the human brain). Eurther research established a basic molecular event associated with shortterm learning habituation caused the sensory neuron to release less glutamate into the synapse sensitization caused the sensory neuron to release more glutamate into the synapse. Thus, the amount of neurotransmitter released into the synapse correlates with the strength of the motor response. The release of glutamate induces an action... 

Exposure to disulfoton can result in inhibition of cholinesterase activity in blood and at nerve synapses of muscles, secretory organs, and nervous tissue in the brain and spinal cord. Central nervous system signs and symptoms include anxiety, restlessness, depression of respiratory and circulatory centers, ataxia, convulsions, and coma. 

Neurotoxic venoms of cobras, mambas, and coral snakes Inhibit the enzyme acetylcholinesterase. - This hydrolase normally breaks down the neurotransmitter acetylcholine within nerve synapses. 

The parasympathetic cholinergic pathway emanating from the vagus nerve exerts the main neuronal control in human airways. The cholinergic efferent nerves synapse in ganglia within the airways, and from there,... 

Figure 3.1 Diagrammatic representation of the functioning of a nerve synapse...

A group of esterases hydrolyze simple oxygen esters. Some of these are designed to hydrolyze a particular ester or small group of esters, while others have a more nonspecific action. Acetylcholinesterase609 611a is specific for acetylcholine (Eq. 12-25), a neurotransmitter that is released at many nerve synapses and neuromuscular junctions (Chapter 30). The acetylcholine, which is very toxic in excess, must be destroyed rapidly to prepare the synapse for transmission of another impulse ... 

The chlorinated hydrocarbons such as DDT act on nerves in a manner that is still not fully understood. One of the largest classes of insecticides acts on the enzyme acetylcholinesterase of nerve synapses. 

We recently proposed a completely electronic model for the excitability of nerve membranes that is based on the assumption of electron-donating, electron-accepting, and electron-storing properties of macromolecules or of protein-lipid complexes which constitute the ionic channels of the nerve membrane (63). This model, which is based on simple physical concepts with easily defined parameters, reproduces the empirical Hodkgin-Huxley equations rather well and also explains how different types of drugs may work on nerves. The model is easily extended to other excitable complexes like the receptor protein complex at nerve synapses and the rodopsin molecules in the retina. Nor is it inconceivable to build a model for the function of smell that is based on electronic triggering of ionic channels which are affected by molecules adsorbed onto or dis-... 

We may now assemble the foregoing information into a molecular description of a few biological processes in which the interaction between water and metal ions plays an important role. First some problems related to signal transfer in nerve cells are discussed. This is followed by some comments on the mechanism operating at nerve synapses in which, in addition to the sodium and potassium ions, a specific transmitter substance and calcium ions take part. 

Degenerating axons in the peripheral nerves can also be examined as described below, and electrophysiological estimates of motor unit number could be informative. Motor units are defined as a single motor neuron (axon) and the muscle fibers its terminals innervate. In motor neuron diseases, the number of motor units is anticipated to decrease as motor neurons die, but the size of motor units may increase with compensatory sprouting and reinnervation (e.g., (1)). Interpretation can be further confounded by factors such as a change in muscle fiber number or innervation of muscle fibers by multiple motor axons. Therefore, the best interpretation results from corroborating evidence from the spinal cord, nerve, synapse, and the muscle. 

The glomerular layer of the olfactory bulb contains a substantial population of dopaminergic neurons. Dopamine acting at D2-like heteroreceptors inhibits glutamate release from terminals of the olfactory sensory neurons and hence may modulate the olfactory nerve synapse (Table 1). 

Berkowicz DA, Trombley PQ (2000) Dopaminergic modulation at the olfactory nerve synapse. Brain Res 855 90-9... 

FIGURE 1.3. The nerve synapse. Illustration copyright 2004 by James P. McCahill. Used with permission. 

Other clinical forms of the disease share many of these signs and symptoms. The presentation and duration of disease are coupled to the relative persistence of the toxin in blocking the release of ACh at peripheral nerve synapses. Although untreated botuhsm is potentially deadly, the availability of antiserum has dramatically reduced the mortality rates for the common clinical manifestations of the disease. Severe cases of foodbome botuhsm may still require ventilatory support for over a month, and neurological symptoms can sometimes persist for more than a year (Mackle et al, 2001). 

Carbofuran is an inhibitor of acetylcholinesterase. Inhibition of acetylcholinesterase activity leads to an increase in acetylcholine at the nerve synapse resulting in excessive cholinergic stimulation. Following intravenous injection of 50pgkg in rats, blood acetylcholinesterase activity was depressed by 83% within 2 min. With oral exposures, acetylcholinesterase activity was depressed by 37% within 15 min of ingestion. Recovery of acetylcholinesterase activity parallels carbofuran elimination. 

The site at which the xenobiotic interacts with the organism at the molecular level is particularly important. This receptor molecule or site of action may be the nucleic acids, specific proteins within nerve synapses or present within the cellular membrane, or it can be very nonspecific. Narcosis may affect the organism not by interaction with a particular key molecule but by changing the characteristics of the cell membrane. The particular kind of interaction determines whether the effect is broad or more specific within the organism and phylogenetically. 

---