Chemical synapse

Describe the mechanism by which chemical synapses function... 

Most of the synapses in the nervous system are chemical synapses in which the presynaptic neuron and the postsynaptic neuron are not in direct contact... 

Figure 5.1 Mechanism of action at a chemical synapse. The arrival of an action potential at the axon terminal causes voltage-gated Ca++ channels to open. The resulting increase in concentration of Ca++ ions in the intracellular fluid facilitates exocytosis of the neurotransmitter into the synaptic cleft. Binding of the neurotransmitter to its specific receptor on the postsynaptic neuron alters the permeability of the membrane to one or more ions, thus causing a change in the membrane potential and generation of a graded potential in this neuron.

The taste bud is a polarized structure with a narrow apical opening, termed the taste pore, and basolateral synapses with afferent nerve fibers. Solutes in the oral cavity make contact with the apical membranes of the TRCs via the taste pore. There is a significant amount of lateral connectedness between taste cells within a bud both electrical synapses between TRCs and chemical synapses between TRCs and Merkel-like basal cells have been demonstrated to occur [39]. Furthermore, there are symmetrical synapses between TRCs and Merkel-like basal cells [39]. In addition, these basal cells synapse with the afferent nerve fiber, suggesting that they may function in effect as interneurons [39]. The extensive lateral interconnections... 

The communication between neurons occurs at either gap junctions (electrical synapses) or chemical synapses with release of neurotransmitters from a presynaptic neuron and their detection by a postsynaptic nerve cell (Fig. 17.1). Neurotransmitters not used in the synaptic cleft are removed promptly by either uptake into adjacent cells, reuptake in the presynaptic neuron, or are degraded by enzymatic systems. 

Neuromuscular junction a chemical synapse between a spinal motor neuron axon and a skeletal muscle fiber. 

All chemical synapses function according to a similar principle. In the area of the synapse, the surface of the signaling cell presynaptic membrane) is separated from the surface of the receiving cell (postsynaptic membrane)... 

Synapses are the contact points of two nerve cells or of a nerve cell with an effector cell (such as a muscle, glandular or sensory cell). It is at the synapse, exactly at the synaptic cleft, where the transfer of information from one cell to the next takes place. It is estimated that the diameter of a synaptic cleft, Le. the distance between the presynaptic membrane (part of the first cell) and the postsvnaptic membrane (part of the second cell), is about 100 300 pm. Depending on the carrier of information, electrical and chemical synapses can be distinguished ... 

In a chemical synapse the two adjacent membranes are not sufficiently close to each other and. in order to pass the information from one cell to the next, the electrical signal is converted transiently into a chemical signal. Most of the synapses in vertebrates are chemical synapses. 

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. 

Figure 4.2 Schematic representation of a chemical synapse, the location within a neuronal network where the transfer of information from one netxon to the next tdces placa by means of neurotransmitters...

Composition and structure of a chemical synapse are shown in a simplified form in Fig.16.2. 

Fig. 16.2. The elementary processes at a chemical synapse, a) In the resting state, the nenrotrans-mitter is stored in vesicles in the presynaptic cell, b) An arriving action potential leads to influx of Ca into the presynaptic cell. Consequently, the vesicles fuse with the presynaptic membrane and the neurotransmitter is released into the synaptic cleft, c) The neurotransmitter diffuses across the synaptic cleft and binds to receptors at the surface of the postsynaptic cell. Ion channel and receptor form a structural unit. The ion channel opens and there is an influx of Na ions into the postsynaptic cell. Recychng takes place in the presynaptic cell and the vesicles are reloaded with neurotransmitter.

The nicotinic acetylcholine receptor is a protein of 290 kD that occins in chemical synapses where conummication between nerve cells and muscle cells takes place. Binding of acetylcholine to the receptor induces opening of the ion chaimel, which is a part of the receptor. Passage of Na and ions through the receptor takes place and depolarization of the postsynaptic cell occurs. The depolarization represents a signal that-according to the nature of the postsynaptic cell—is processed in various ways. 

The communication between neurons in the CNS occurs through chemical synapses in the majority of cases. (A few instances of electrical coupling between neurons have been documented, and such coupling may play a role in synchronizing neuronal discharge. However, it is unlikely that these electrical synapses are an important site of drug action.) The events involved in synaptic transmission can be summarized as follows. 

Gap junctions in synapses. Not all neurons communicate via chemical synapses. Gap junctions, which are found in both neurons, astrocytes, and other cells, serve as electrical synapses. Thus, heart cells are all electrically coupled together by gap junctions.606-608 Gap junctions are formed with the aid of hexameric connexons, which are present in each of the opposed membranes and are aligned one with the other (Fig. 1-15F,G).607 609 610 There may be thousands of connexons in a single gap junction, which resemble ion channels in appearance but contain pores 1.5 nm in diameter. They are formed from 26- to 43- kDa... 

The chemical synapse is a highly specialized structure that has evolved for exquisitely controlled voltage-dependent secretions. The chemical messengers, stored in vesicles, are released from the presynaptic cell following the arrival of an action potential that triggers the vesicular release into the presynaptic terminal. Once released from the vesicles, the transmitter diffuses across a narrow synaptic cleft, then binds to specific receptors in the postsynaptic cell, and finally initiates an action potential event in the nerve-muscle cell membrane by triggering muscle contractions. 

Reuptake. After the neurotransmitter is released, some chemical synapses terminate activity primarily by transmitter reuptake. Reuptake involves the movement of the transmitter molecule back into the presynaptic terminal. A drug that impairs the reuptake of transmitter allows more of it to remain in the synaptic cleft and continue to exert an effect. Consequently, blocking reuptake actually increases activity at the synapse. For instance, tricyclic antidepressants (see Chapter 7) impair the reuptake mechanism that pumps amine neurotransmitters back into the presynaptic terminal, which allows the transmitter to continue to exert its effect and prolong activity at the synapse. 

As described in Chapter 4, regulatory G proteins act as an intermediate link between receptor activation and the intracellular effector mechanism that ultimately causes a change in cellular activity. In the case of opioid receptors, these G proteins interact with three primary cellular effectors calcium channels, potassium channels, and the adenyl cyclase enzyme.27 At the presynaptic terminal, stimulation of opioid receptors activates G proteins that in turn inhibit the opening of calcium channels on the nerve membrane.65 Decreased calcium entry into the presynaptic terminal causes decreased neurotransmitter release because calcium influx mediates transmitter release at a chemical synapse. At the postsynaptic neuron, opioid receptors are linked via G proteins to potassium channels, and... 

Bone cells are electrically active [10, 11, 24, 121, 170]. In addition to permitting the intercellular transmission of ions and small molecules, gap junctions exhibit both electrical and fluorescent dye transmission [93, 183, 187, 133], Gap junctions are electrical synapses, in contradistinction to intemeur-onal, chemical synapses and, significantly, they permit bi-directional signal traffic (e.g., biochemical, ionic, electrical etc.). In a physical sense, the CCN represents the hard wiring [30, 140, 141, 150] of bone tissue. 

In this chapter, we will review the evidence suggesting a role for specific synaptic vesicle-associated proteins in schizophrenia. First, we present a brief overview of the synaptic vesicle cycle in the broader context of synaptic neurotransmission at chemical synapses. We then describe the experimental evidence linking specific molecular components of the synaptic vesicle to schizophrenia. Since not all synaptic vesicle proteins have been studied in relationship to schizophrenia, this review focuses only on those proteins for which such an effort was made. Finally, we describe the potential roles these proteins could play in the context of current etiological theories of schizophrenia, and discuss the relevance of the experimental findings in the context of this enigmatic disorder. 

Neurotransmission at chemical synapses is carried out by a complex sequence of events. Initially, an action potential arrives at the presynaptic terminal, inducing a rapid, transient influx of Ca2+ locally ( Figure 2.4-1). 

Chemical synapses, for example between two neurones or between a neurone and a muscle fibre transmission is slower since there is a delay of 0.5 ms because of a gap of 20 nm between the cells. For transmission to occur the chemical transmitter must be made and stored in vesicles at the presynaptic side. The transmitter is ready to be released whenever an action potential arrives at the presynaptic nerve. Because the transmitter is only on one side of the synapse, the impulse can move in only one direction. 

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