Postsynaptic cell

Synaptic Transmission. Figure 1 Synaptic transmission. The presynaptic terminal contains voltage-dependent Na Superscript and Ca2+ channels, vesicles with a vesicular neurotransmitter transporter VNT, a plasmalemmal neurotransmitter transporter PNT, and a presynaptic G protein-coupled receptor GPCR with its G protein and its effector E the inset also shows the vesicular H+ pump. The postsynaptic cell contains two ligand-gated ion channels LGIC, one for Na+ and K+ and one for Cl-, a postsynaptic GPRC, and a PNT. In this synapse, released transmitter is inactivated by uptake into cells. 

All these postsynaptic events last only for a few milliseconds synaptic transmission through LGICs is fast. When the postsynaptic cell membrane is sufficiently depolarized, voltage-dependent Na+ channels open and an action potential is generated. 

GPCRs are proteins that span the postsynaptic cell membrane seven times (heptahelical receptors). Small ligands are usually bound within a pocket formed by the... 

These cascades of reactions need time in the range of seconds synaptic transmission through GPCRs is slow. All further postsynaptic changes depend on the type of postsynaptic cell. For example activation of 32-adrenoceptors causes in the heart an increase of the rate and force of contraction in skeletal muscle glycogenolysis and tremor in smooth muscle relaxation in bronchial glands secretion and in sympathetic nerve terminals an increase in transmitter release. 

Extracellular degradation removes acetylcholine, the neuropeptides and ATP. Acetylcholine is rapidly hydrolyzed to choline and acetate by acetylcholinesterase. The enzyme is localized in both the presynaptic and the postsynaptic cell membrane and splits about 10,000 molecules of acetylcholine per second. 

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

Presynaptic events during synaptic transmission are rapid, dynamic and interconnected. The time between Ca2+ influx and exocytosis in the nerve terminal is very short. At the frog NMJ at room temperature, 0.5-1 ms elapses between the depolarization of the nerve terminal and the beginning of the postsynaptic response. In the squid giant synapse, recordings can be made simultaneously in the presynaptic nerve terminal and in the postsynaptic cell. Voltage-sensitive Ca2+ channels open toward the end of the action potential. The time between Ca2+ influx and the postsynaptic response as measured by the postsynaptic membrane potential is 200 ps (Fig. 10-7). However, measurements made with optical methods to record presynaptic events indicate a delay of only 60 ps between Ca2+ influx and the postsynaptic response at 38°C [21]. 

Thus, the mechanistic properties of the NMDA receptor can help account for the properties of temporal specificity, cooperativity, and associativity of LTP. They can also explain why both high-frequency stimulation (100 Hz) and pairing low-frequency stimulation with postsynaptic depolarization can induce LTP. The occurrence of presynaptic activity followed by postsynaptic activity determines a temporal sequence and specificity. To generate sufficient depolarization in the postsynaptic cell to expel Mg2+ from NMDAR channels usually requires cooperative depolarization at many synapses. Moreover, the requirement of postsynaptic depolarization also underlies associativity since the depolarization caused by the strongly activated synapses can relieve the Mg2+ blockade of the NMDA receptors on weakly activated synapses. 

Ionotropic receptors (bottom left) are ligand-gated ion channels. When they open as a result of the transmitter s influence, ions flow in due to the membrane potential (see p. 126). If the inflowing ions are cations (Na"", C, Ca ""), depolarization of the membrane occurs and an action potential is triggered on the surface of the postsynaptic cell. This is the way in which stimulatory transmitters work (e.g., acetylcholine and glutamate). By contrast, if anions flow in (mainly Cl ), the result is hyperpolarization of the postsynaptic membrane, which makes the production of a postsynaptic action potential more dif cult. The action of inhibitory transmitters such as glycine and GABA is based on this effect. 

A completely different type of effect is observed in metabotropic receptors (bottom right). After binding of the transmitter, these interact on the inside of the postsynaptic membrane with Gproteins (see p. 384), which in turn activate or inhibit the synthesis of second messengers. Finally, second messengers activate or inhibit protein kinases, which phosphorylate cellular proteins and thereby alter the behavior of the postsynaptic cells (signal transduction see p.386). 

Like all signaling substances, neurotransmitters (see p. 352) act via receptor proteins. The receptors for neurotransmitters are integrated into the membrane of the postsynaptic cell, where they trigger ion inflow or signal transduction processes (see p. 348). 

Metabotropic receptors (right half of the table) are coupled to G proteins (see p. 386), through which they influence the synthesis of second messengers. Receptors that work with type Gj proteins (see p. 386) increase the cAMP level in the postsynaptic cell ([cAMP] I), while those that activate Gj proteins reduce it ([cAMP] i ). Via type Gq proteins, other receptors increase the intracellular Ca "" concentration ([Ca j ). 

The muscarinic ACh receptors influence the cAMP level in the postsynaptic cells (Mi, M3 and Ms increase it, while subtypes M2 and M4 reduce it). 

Substances that block the serine residue in the active center of acetylcholinesterase [2j—e.g., the neurotoxin E605 and other organophosphates—prevent ACh degradation and thus cause prolonged stimulation of the postsynaptic cell. This impairs nerve conduction and muscle contraction. Curare, a paralyzing arrow-poison used by South American Indians, competitively inhibits binding of ACh to its receptor. 

Pharmacology The precise mechanism by which tiagabine exerts its antiseizure effect is unknown, although it is believed that it blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of postsynaptic cells. 

Presynaptic or prejunctional receptors are located on the presynaptic nerve endings and function to control the amount of transmitter released per nerve impulse and in some instances to affect the rate of transmitter synthesis through some as yet undetermined feedback mechanism. For instance, during repetitive nerve stimulation, when the concentration of transmitter released into the synaptic or junctional cleft is relatively high, the released transmitter may activate presynaptic receptors and thereby reduce the further release of transmitter. Such an action may prevent excessive and prolonged stimulation of the postsynaptic cell. In this case, the activation of the presynaptic receptor would be part of a negative feedback mechanism... 

Recovery of postsynaptic cell from the effects of the transmitter None known Succinylcholine... 

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). 

The functional significance of this drug-receptor interaction is that the receptor complex regulates the entrance of chloride into the postsynaptic cells. The increase in chloride conductance mediated by GABA is intensified by the benzodiazepines. This facilitation of GABA-induced chloride conductance results in greater hyperpolarization of these cells and therefore leads to diminished synaptic transmission. 

The neuron receiving the input (postsynaptic cell) can be modulated via two different types of receptors [see... 

This colored electron microscope image depicts a synapse between the presynaptic embrane, shown in pink, and the postsynaptic membrane, shown in green. The slightly thickened area between the pre- and postsynaptic cells is part of the synapse. Small circles in the presynaptic cell are vesicles containing neurotransmitters. [Dr. Dennis Kunke / Visuals Dniimited]... 

Receptors are proteins usually embedded in the cell s membrane. A neurotransmitter such as dopamine docks at its receptor, activating it and initiating some kind of response in the postsynaptic cell. The response depends on the type of receptor, and there are a number of different ones for most neurotransmitters. Researchers have found five dopamine receptors the one affected by chlorpromazine and similar drugs is known as D. These drugs prevent dopamine from activating the receptor. 

PDZ domains were first identified in proteins of postsynaptic cells and their designation comes from their occurrence in the proteins PSD-95, DlgA and ZO-1 (see Saras and Heldin, 1996). In the meantime, PDZ domains have been found in many other proteins, particularly in proteins that form structures in the cell membrane (e.g. in ion channels) and in signal proteins (review Craven and Brett, 1997). PDZ domains recognize short peptide sequences with a C-terminal hydrophobic residue and a free carboxyl group, such as the E(S/T)DV motif at the C terminus of certain subunits of ion channels. 

The protein PSD-95 is an example of a PDZ-containing protein (review Craven and Bredt, 1998). PSD-95 is found in postsynaptic cells where, via its PDZ domains, it mediates interactions with intracellular domains of receptors such as the NMDA receptor (see 16.4.2.1). The InaD protein which is composed solely of PDZ domains has an adaptor function in the vision process in Drosophila (see 8.2.5). 

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