Post-synaptic cell

Nerve cells Nerve cells, or neurons, consist of a cell body from which the dendrites and axon extend. The dendrites receive information from other cells the axon passes this information on to another cell, the post-synaptic cell. The axon is covered in a myelin membranous sheath except at the nodes of Ranvier. The axon ends at the nerve terminal where chemical neurotransmitters are stored in synaptic vesicles for release into the synaptic cleft. 

Neurotransmitters Chemical neurotransmitters, such as acetylcholine, the biogenic amines and small peptides, are stored in the pre-synaptic nerve terminal in synaptic vesicles. When the action potential reaches the nerve terminal it causes the synaptic vesicles to fuse with the plasma membrane in a Ca2+-dependent manner and to release their contents by exocytosis. The neurotransmitter then diffuses across the synaptic cleft, binds to specific receptors on the post-synaptic cell membrane and initiates a response in that cell. 

Removal of norepinephrine Norepinephrine may (1) diffuse out of the synaptic space and enter the general circulation, (2) be metabolized to O-methylated derivatives by post-synaptic cell membrane-associated catechol O-methyltransferase (COMT) in the synaptic space, or (3) be recaptured by an uptake system that pulls the norepinephrine back into the neuron. The uptake by the neuronal membrane involves a sodium-potassium activated ATPase that can be inhibited by tricyclic antidepressants such as imipramine (see p. 119), or by cocaine (see Figure 6.3). 

Synaptic Clearance Antagonists. By preventing the removal of naturally-released transmitter from the region of its receptors, the effect of the neuromesssenger on the receiving cell will be prolonged and intensified. There are three principal routes by which neuromessengers are removed from the synaptic cleft (i) enzymatic destruction of the transmitter (e.g., acetylcholine (ACh) which is hydrolyzed in the synaptic cleft by acetylcholinesterase) (ii) uptake into pre- and post- synaptic cells by membrane-associated pumps that have substantial specificty for molecules they will carry (iii) diffusion away from the cleft. 

All catecholamine receptors are metabotropic. They act by initiating metabohc processes affecting cellular functions. P-adrenergic receptors, receptors for epinephrine, and norepinephrine act by stimulatory G proteins to increase cAMP in the post-synaptic cell. cAMP binds to and activates protein-kinase enzyme. 

More than 30 different substances have been proven or proposed to act as neurotransmitters. Neurotransmitters are either excitatory or inhibitory. As noted, excitatory neurotransmitters (e.g., glutamate and acetylcholine) open sodium channels and promote the depolarization of the membrane in another cell (either another neuron or an effector cell, such as a muscle cell). If the second (post-synaptic) cell is a neuron, the wave of depolarization (referred to as an action potential) triggers the release of neurotransmitter molecules as it reaches the end of the axon. (Most neurotransmitter molecules are stored in numerous membrane-enclosed synaptic vesicles.) When the action potential reaches the nerve ending, the neurotransmitter molecules are released by exocytosis into the synapse. If the postsynaptic cell is a muscle cell, sufficient release of excitatory neurotransmitter molecules results in muscle contraction. Inhibitory neurotransmitters (e.g., glycine) open chloride channels and make the membrane potential in the postsynaptic cell even more negative, that is, they inhibit the formation of an action potential. 

Nicotinic receptors act by the transmitter simply opening a pore in the post-synaptic neuron membrane and thus allowing a flow of ions which changes the electrical characteristics of that cell. Muscarinic receptors operate differently. These act via various G-proteins to change both the electrical and more complex metabolic activities of the post-synaptic cell. To date, five different muscarinic receptor sub-types have been discovered ... 

In other words, the odd-numbered receptors excite the post-synaptic cell whilst the even-numbered muscarinic receptors decrease its electrical activity. 

Human Hcrt-1 is a 33-amino-acid-chain peptide and is identical to the mouse, rat, bovine and porcine peptides. Hcrt-2 in humans is a 28-amino-acid chain which has two different substitutions compared with rodent Hcrt-2 and one compared with porcine and canine Hcrt-2s. Clearly, these peptides are strongly conserved, suggesting important functions. Both peptides have similar affinities for the hcrtr2 receptor but Hcrt-1 has greater affinity than Hcrt-2 for the human hcrtrl receptor. In all experiments carried out so far hypocretins have had excitatory effects on post-synaptic cells. The noradrenergic locus coeruleus neurons discussed previously are densely packed with hcrtrl receptors, but not hcrtr2 receptors. 

At synapses impulses are transmitted by neurotransmitters released from the axon terminal of the presynaptic cell and subsequently bound to specific receptors on the post-synaptic cell (see Figure 7-31). 

Cytosolic proteins that contain multiple PDZ or other protein-binding domains cluster receptors and other proteins within the plasma membrane, as occurs in post-synaptic cells (see Figure 13-9). 

Neurotransmitters and neuropeptides Neurotransmitters are released from the presynaptic cell into the tiny volume defined by the synaptic cleft. Individual neuron contains only very small quantities of the transmitter. The released transmitter then diffuses across the cleft and binds to receptors on the post-synaptic cell. The diffusion across the short distance that separate pre- and post-synaptic neurons is fast enough to allow rapid communication between nerves or between nerve and muscle at a neuromuscular junction. acetylcholine, adrenaline noradrenaline, dopamine, serotonin, glutamate, glycine, GABA, enkephalins, substance P, angiotensin II, somatostatin... 

Neurotransmitter A low-molecular-weight substance that is released from an axon terminal in response to the arrival of an action potential and then diffuses across the synapse to influence the post-synaptic cell, which may be either another neuron or a muscle or gland cell. 

Chloride channels represent the only anionic channel of interest for analgesic development. These channels often play an important role in neural excitability and therefore are important in the roles of several neurotransmitters including GABA and glycine. Hyperpolarization of the post-synaptic cell body leads to a less excitable nerve fiber and the resultant loss of sensory transmission through select fibers. Through several 20 cascading events, interactions at the Cl" channel result in a hyperpolarization by the inward rush of Cl. 

All of the known neurotransmitters synthesised in mammalian neurons share certain chemical properties all are low-molecular-weight, water-soluble compounds which are ionised at the pH of body fluids. All are synthesised primarily in the parts of the neuron (the synaptic bulbs, or nerve terminals) which form synaptic contacts with the cells to which the neuron transmits signals (the post-synaptic cells), and all are stored within subcellular organelles (synaptic vesicles) or are attached to cytoplasmic proteins, prior to being released into a synapse (Fig. 1). Release occurs when the neuron that synthesised the neurotransmitter is depolarised. Thereafter, some of... 

Release of quanta of the transmitter by unknown physiological processes and association of the transmitter with the receptor macromolecule on the post-synaptic cell membrane. This... 

---