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Monday, March 7, 2011

Synaptic transmission

Synaptic transmission
The sequence of events that result in neurotransmission of information from one nerve cell to another across the synapses begins with a wave of depolarization which passes down the axon and results in the opening of the voltage-sensitive calcium channels in the axonal terminal. These channels are frequently concentrated in areas which correspond to the active sites of neurotransmitter release. A large (up to 100 mM) but brief rise in the calcium concentration within the nerve terminal triggers the movement of the synaptic vesicles, which contain the neurotransmitter, towards the synaptic membrane. By means of specific membrane-bound proteins (such as synaptobrevin from the neuronal membrane and synaptotagrin from the vesicular membrane) the vesicles fuse with the neuronal membrane and release their contents into the synaptic gap by a process of exocytosis. Once released of their contents, the vesicle membrane is reformed and recycled within the neuronal terminal. This process is completed once the vesicles have accumulated more neurotransmitter by means of an energy-dependent transporter on the vesicle membrane.
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.There are two major types of receptor which are activated by neurotransmitters. These are the ionotropic and metabotropic receptors. The former receptor type is illustrated by the amino acid neurotransmitter receptors for glutamate, gamma-aminobutyric acid (GABA) and glycine, and the acetylcholine receptors of the nicotinic type. These are examples of fast transmitters in that they rapidly open and close the ionic channels inthe neuronal membrane. Peptides are often co-localized with these fast transmitters but act more slowly and modulate the excitatory or inhibitory actions of the fast transmitters. By contrast to the amino acid neurotransmitters, the biogenic amine transmitters such as noradrenaline, dopamine and serotonin, and the non-amine transmitter acetylcholine acting on the muscarinic type of receptor, activate metabotropic receptors. These receptors are linked to intracellular second messenger systems by means of G (guanosine triphosphate-dependent) proteins. These comprise the slow transmitters because of the relatively long time period required for their physiological response to occur. It must be emphasized however that a number of metabotropic receptors have recently been identified that are activated by fast transmitters so that the rigid separation of these receptor types is somewhat blurred. Over 50 different types of neurotransmitter have so far been identified in the mammalian brain and these may be categorized according to their chemical structure.

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