Neurotransmission postsynaptic

The nicotinic acetylcholine (ACh) receptor mediates neurotransmission postsynaptically at the neuromuscular junction and peripheral autonomic ganglia in the central nervous system (CNS), it largely controls release of neurotransmitters from presynaptic sites. The receptor is called the nicotinic acetylcholine receptor because it is stimulated by both the neurotransmitter ACh and the alkaloid nicotine. 

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. 

Although, to our knowledge, the effects of inhalation of amyl nitrite or butyl nitrite on glutamatergic neurotransmission have not been studied, NO, the potent compound that mediates the peripheral effects of nitrites in blood vessels, if released in the CNS when nitrites are inhaled, may potentially affect the glutamatergic system. NO has been reported to act directly on the postsynaptic NMDA receptor, where it can increase or decrease NMDA-mediated currents and subsequent calcium influx (Aizenman et al. 1990 Dingledine et al. 1999 Manzoni et al. 1992). 

Virtually all types of drug that have been shown to be effective in major depression exert profound effects on the functioning of the serotoninergic or noradrenergic systems, or both. Although some treatments have been shown to decrease the sensitivity of certain postsynaptic 5-HT and NE receptors, it is generally believed that it is an enhancement of neurotransmission in these systems that is responsible for the improvement of the core symptoms of depression. For instance, long-term administration of tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) decreases the density of (3-adrenoceptors and cortical 5-HT2 receptors (Blier and Abbott 2003). 

Neurotransmission in autonomic ganglia is more complex than depolarization mediated by a single transmitter 190 Muscarinic receptors are widely distributed at postsynaptic parasympathetic effector sites 190 Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber 191 Competitive blocking agents cause muscle paralysis by preventing access of acetylcholine to its binding site on the receptor 191... 

To illustrate some of the roles played by protein phosphorylation in the regulation of nervous system function, some well characterized neuronal phosphoproteins and some aspects of neurotransmission regulated by phosphorylation in the pre- and postsynaptic compartments are discussed in detail. 

Ammonia has deleterious effects on brain function by direct and indirect mechanisms. Concentrations of ammonia in the 1-2 mmol/1 range, equivalent to those reported in the brain in liver failure, impair postsynaptic inhibition in cerebral cortex and brainstem by a direct effect on Cl extrusion from the postsynaptic neuron. Millimolar concentrations of ammonia also inhibit excitatory neurotransmission. Synaptic transmission from Schaffer collaterals to CA1 hippocampal neurons is reversibly depressed by 1 mmol/1 ammonia, and the firing of CA1 neurons by iontophoretic application of glutamate is inhibited by 2 mmol/1 ammonia [10],... 

It is now possible to image not only postsynaptic, but pre-synaptic and intrasynaptic neurotransmission (Fig. 58-5). Presynaptic sites, such as the dopamine transporter and the serotonin transporter the presynaptic dopamine vesicular transporter (VMAT-2) and the acetylcholine transporter extrasynaptic sites such as the enzymes which break down neurotransmitters, e.g. MAO A and MAO B with radioligands that bind to post or pre-synaptic sites, i.e. dopamine competing with radioligands such as UC raclopride (see Fig. 58-9) (PET (Fig. 58-10) can be measured under basal conditions or following drugs which either decrease (e.g. AMPT) or increase (e.g. intravenous amphetamine) intrasynaptic dopamine. 

It therefore appears that inhibitory somatodendritic 5-HTia receptor function is reduced by GR activation, leading to an enhancement of 5-HT neurotransmission generally, while the effects of corticosteroids on postsynaptic receptor function depends on the level of circulating corticosteroid differentially activating MR or GR receptors. 

In the adrenal medulla and the ganglia of parasympathetic and sympathetic nerves, the neurotransmission is mediated by acetylcholine. On the postsynaptic membranes the transmitter activates the neuronal-type of the nicotinic acetylcholine receptor. This receptor type is in fact a sodium channel, its activation leads to a sodium influx and a membrane depolarization. A pharmacological interference at the... 

Like in the neuromuscular junction the neurotransmission can be inhibited either by receptor blockade (non-depolarizing) or by overstimulation (depolarizing) of the receptors. The alkaloid nicotine, in low doses, stimulates ganglia and the adrenaline release from the adrenal medulla. High doses lead to a continuous depolarization of the postsynaptic membrane and thereby to an inactivation of the neurotransmission. All ganglion blockers in clinical use were synthetic amines of the nondepolarizing type trimethaphan, hexamethonium and mecamylamide. 

Like in the parasympathetic and ganglionic neurotransmission, the eliminating enzyme acetylcholine esterase is present at the postsynaptical membrane where it very efficiently reduces the free concentration of the transmitter. 

Fig. 2. Schematic drawing of the adrenergic neurotransmission. Dependent on the target organ, the postsynaptic, G-protein-coupled receptors are of the a -, 2- or /Sj-adrenoceptor subtype. A presynaptic 2-adrenoceptor acts as an inhibitory autoreceptor. The predominant elimination pathway of the transmitter noradrenaline (NA) is the neuronal re-uptake...

Analogous to 5-HT ia KO mice, the neural mechanisms underlying increased anxiety-related behavior and reduced exploratory locomotion in mice with a disruption of the 5-HTT gene may relate to excess serotonergic neurotransmission which is expected to cause enhanced activation of postsynaptic 5-HT receptors. Both in vivo microdialysis in striatum and in vivo chronoamperom-etry in hippocampus revealed that 5-HTT null-mutant mice exhibit an approximately fivefold increase in extracellular concentrations of 5-HT and an absence of transporter-mediated clearance, although brain tissue 5-HT concentrations are markedly reduced by 40%-60% (Bengel et al. 1998). 

Transmission through autonomic ganglia is more complex than neurotransmission at the neuromuscular and postganglionic neuroeffector junctions and is subject to numerous pharmacological and physiological influences. In some ganglionic synapses, especially at parasympathetic ganglia, there is a simple presynaptic to postsynaptic cell relationship in others, the presynaptic to postsynaptic cell relationship may involve neurons interposed between the presynaptic and postsynaptic elements (interneurons). 

During a laboratory demonstration to depict the complexity of neurotransmission in autonomic ganglia, Professor Smith sets up an anesthetized mammalian preparation in which she is recording postsynaptic events following the electrical stimulation of preganglionic sympathetic nerves. This demonstrates a complex action potential that consists of a fast EPSP followed by a slow IPSP followed by a slow EPSP and finally by a late very slow EPSP. 

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