Neurotransmitter signalling

Stopping Neurotransmission. Turning off the neurotransmitter signal once it has been released into the synapse is critical to successful communication between nerve cells. This is of paramount importance because unbridled stimulation can be harmful to nerve cells. For example, one of the problems in the minutes and hours following a stroke is that nerve cells near the stroke area can literally be stimulated to death. In fact, some of the new medications used to minimize damage to the brain after a stroke act by literally calming the cells in the brain. Thus, signal termination is a critically important aspect of neurotransmission. 

As we noted earlier, when the neurotransmitter is released from the axon terminal into the synapse, it is free to diffuse across the synapse to bind the receptors on the neighboring nerve cell. However, other fates may await the neurotransmitter once it s released into the synapse. In general, these other processes act to terminate neurotransmission by preventing the neurotransmitter from reaching the receptor on the adjacent nerve cell. There are, in fact, five distinct mechanisms for terminating the neurotransmitter signal once it has been released into the synapse. 

Reuptake. The nerve cell that released the neurotransmitter also has what are called reuptake sites on its surface. These reuptake sites are actually transporter proteins that are specific to each type of neurotransmitter. They act like miniature vacuum cleaners to retrieve the neurotransmitter from the synapse. The neurotransmitter is removed from the synapse at the reuptake site and returned to the inside of the nerve cell s axon terminal. Although the reuptake process recycles the neurotransmitter molecules for future use, the process does, in fact, serve to terminate the current neurotransmitter signal. 

Only the first type of neurotransmitter release mediates the fast point-to-point synaptic transmission process at classical synapses (sometimes referred to as wiring transmission). All of the other types of neurotransmitter release effect one or another form of volume transmission whereby the neurotransmitter signal acts diffusely over more prolonged time periods (Agnati et al., 1995). Of these volume transmitter pathways, the time constants and volumes involved differ considerably. For example, diffusible neurotransmitters such as nitric oxide act relatively briefly in a localized manner, whereas at least some neuropeptides act on the whole brain, and can additionally act outside of it (i.e., function as hormones). There is an overlap between wiring and volume neurotransmission in that all classical neurotransmitters act as wiring transmitters via ionotropic receptors, and also act as volume transmitters via G-protein-coupled receptors. Moreover, neuromodulators in turn feed back onto classical synaptic transmission. 

G protein-coupled receptors function as adapters between the virtually boundless multitude and variety of extracellular hormone and neurotransmitter signals and the lower (yet still considerable) number of intracellular G-proteins. Therefore, it is very common to have receptors for multiple transmitters or hormones converge onto the same type of G protein and thus trigger the same response. E g., glucagon and epinephrine both activate adenylate cyclase in the liver, through separate receptors but the very same G protein. 

Gietzen DW. 2000. Amino acid recognition in the central nervous system. Neural and Metabolic Control of Macro-nutrient Intake, Chapter 23. Berthoud HR, Seeley RJ, editors. New York CRC Press pp. 339-357. (Includes pharmacology of neurotransmitter signaling in the APC down-stream of AA sensing)... 

Allen JA, Halverson-Tamboli RA, Rasenick MM. Lipid raft microdomains and neurotransmitter signalling. 

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