Neurotransmitters postsynaptic membrane receptors

A variety of methods have been developed to study exocytosis. Neurotransmitter and hormone release can be measured by the electrical effects of released neurotransmitter or hormone on postsynaptic membrane receptors, such as the neuromuscular junction (NMJ see below), and directly by biochemical assay. Another direct measure of exocytosis is the increase in membrane area due to the incorporation of the secretory granule or vesicle membrane into the plasma membrane. This can be measured by increases in membrane capacitance (Cm). Cm is directly proportional to membrane area and is defined as Cm = QAJV, where Cm is the membrane capacitance in farads (F), Q is the charge across the membrane in coulombs (C), V is voltage (V) and Am is the area of the plasma membrane (cm2). The specific capacitance, Q/V, is the amount of charge that must be deposited across 1 cm2 of membrane to change the potential by IV. The specific capacitance, mainly determined by the thickness and dielectric constant of the phospholipid bilayer membrane, is approximately 1 pF/cm2 for intracellular organelles and the plasma membrane. Therefore, the increase in plasma membrane area due to exocytosis is proportional to the increase in Cm. 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

Nitric oxide (NO) and carbon monoxide are atypical neurotransmitters. They are not stored in synaptic vesicles, are not released in by exocytosis, and do not act at postsynaptic membrane receptor proteins. NO is generated in a single step from the amino acid arginine through the action of the NO synthase (NOS). The form of NOS initially purified was designated nNOS (neuronal NOS), the macrophage form is termed inducible NOS (iNOS), and the endothelial from is called eNOS. 

Neurotransmitters are recognized by receiving neurons, neuromuscular junctions, or end effector organs via receptors that lie on the postsynaptic membrane. Receptors are generally selective for the neurotransmitter that they bind. The type of signaling that is characteristic of a given neurotransmitter is usually the result of the form of receptor to which it binds. For example, some receptors, like the nicotinic acetylcholine receptor found in neuromuscular junctions, are ion channels. The stimulation of the nicotinic... 

In the CNS, receptors at most synapses are coupled to ion channels, that is, binding of the neurotransmitter to the postsynaptic membrane receptors results in a rapid but transient opening of ion channels. Open channels allow ions inside and outside the cell membrane to flow down their concentration gradients. The resulting change in the ionic composition across the membrane of the neuron alters the postsynaptic potential, producing either depolarization or hyperpolarization of the postsynaptic membrane, depending on the specific ions that move and the direction of their movement. 

Acetylcholinesterase is a component of the postsynaptic membrane of cholinergic synapses of the nervous system in both vertebrates and invertebrates. Its structure and function has been described in Chapter 10, Section 10.2.4. Its essential role in the postsynaptic membrane is hydrolysis of the neurotransmitter acetylcholine in order to terminate the stimulation of nicotinic and muscarinic receptors (Figure 16.2). Thus, inhibitors of the enzyme cause a buildup of acetylcholine in the synaptic cleft and consequent overstimulation of the receptors, leading to depolarization of the postsynaptic membrane and synaptic block. 

The presence of specific receptors for the neurotransmitter on the postsynaptic membrane, such that application of the neurotransmitter to the synapse mimics the effects of presynaptic nerve stimulation... 

The postsynaptic membrane opposite release sites is also highly specialized, consisting of folds of plasma membrane containing a high density of nicotinic ACh receptors (nAChRs). Basal lamina matrix proteins are important for the formation and maintenance of the NMJ and are concentrated in the cleft. Acetylcholinesterase (AChE), an enzyme that hydrolyzes ACh to acetate and choline to inactivate the neurotransmitter, is associated with the basal lamina (see Ch. 11). 

Another example of molecular communication is found in a neuronal synapse, which is a communication junction between two neurons as shown in Fig.2. The presynaptic membrane releases the neurotransmitter molecule that is recognized and captured by the receptor located on the surface of the postsynaptic membrane. 

Figure 21.1 A schematic drawing of a synapse. The synaptic terminal is shown activated. Synaptic vesicles are fusing with the presynaptic membrane and releasing a neurotransmitter that diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane. This triggers a new nerve impulse. (Redrawn from D. Voet and J. G. Voet, Biochemistry, 3rd edn, 2004. Donald and Judith G. Voet. Reprinted with permission of John Wiley and Sons, Inc.)...

After release by exocytosis, the neurotransmitter diffuses across the cleft and binds to a receptor on the membrane of the postsynaptic neurone. The binding affects an ion channel, which changes the polarisation of the postsynaptic membrane (see below). 

Figure 14.10 Diagrammatic representation of regulation of the opening of an ion channel by phosphoiylation of a protein in the channel. The neurotransmitter-receptor complex functions as a nucleotide exchange factor to activate a G-protein which then activates a protein kinase. This is identical to control of G-proteins in the action of hormones (Chapter 12, see Figure 12.21). Phosphorylation of a protein in the ion channel opens it to allow movement of Na+ ions. The formation of the complex, activation of the G-protein and the kinase takes place on the postsynaptic membrane. An example of the structural organisation and the involvement of a G-protein is shown in Chapter 12 (Figure 12.6).

The neurotransmitters diffuse across the synaptic cleft in a fraction of a millisecond where, on reaching the postsynaptic membrane on an adjacent neuron, they bind to specific receptor sites and trigger appropriate physiological responses. 

Neurotransmitters can either excite or inhibit the activity of a cell with which they are in contact. When an excitatory transmitter such as acetylcholine, or an inhibitory transmitter such as GABA, is released from a nerve terminal it diffuses across the synaptic cleft to the postsynaptic membrane, where it activates the receptor site. Some receptors, such as the nicotinic receptor, are directly linked to sodium ion channels, so that when acetylcholine stimulates the nicotinic receptor, the ion channel opens to allow an exchange of sodium and potassium ions across the nerve membrane. Such receptors are called ionotropic receptors. 

Each neuron usually releases only one type of neurotransmitter. Neurons that release dopamine are referred to as dopaminergic, for example, while those that release acetylcholine are cholinergic, etc. The transmitters that are released diffuse through the synaptic cleft and bind on the other side to receptors on the postsynaptic membrane. These receptors are integral membrane proteins that have binding sites for neurotransmitters on their exterior (see p. 224). 

Ionotropic receptors are ligand-gated ion channels (left half of the table). The receptors for stimulatory transmitters (indicated in the table by a ) mediate the inflow of cations (mainly Na""). When these open after binding of the transmitter, local depolarization of the postsynaptic membrane occurs. By contrast, inhibitory neurotransmitters (GABA and glycine) allow cr to flow in. This increases the membrane s negative resting potential and hinders the action of stimulatory transmitters hyperpolarization, 0). 

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... 

Besides the differentiation of cholinergic and adrenergic neurons in these systems, there is also a variation in the protein receptors with which the neurotransmitters complex at the postsynaptic membrane. 

One of the best-understood examples of a ligand-gated receptor channel is the nicotinic acetylcholine receptor (see Fig. 11-51). The receptor channel opens in response to the neurotransmitter acetylcholine (and to nicotine, hence the name). This receptor is found in the postsynaptic membrane of neurons at certain synapses and in muscle fibers (myocytes) at neuromuscular junctions. 

Was this your answer A neurotransmitter is a small organic molecule released by a neuron into a synaptic cleft. It influences neighboring tissue, such as the postsynaptic membrane of a neuron on the opposite side of tbe cleft, by binding to receptor sites. 

Classically, it has been held that this neurotransmitter-receptor complex initiates a process that reconverts the chemical message back into an electrical impulse in the second nerve. This is certainly true for rapid-onset neurotransmitters and can explain the initial actions of some slow-onset neurotransmitters as well. However, it is now known that the postsynaptic neuron has a vast repertoire of responses beyond just whether it changes its membrane polarization to make it more or less likely to fire. Indeed, many important biochemical processes are triggered in the postsynaptic neuron by neurotransmitters occupying their receptors. Some of these begin within milliseconds, whereas others can take days to develop (Figs. 1 — 11 to 1 — 13). 

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