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Title: Neurotransmission Post by CJohnson on Jun 12th, 2003, 1:57pm Messages travel through the nervous system by an electrochemical process. In this process, chemicals (molecules) are released from the cell body of a neuron, travel down the axon, and are released into the synaptic cleft from the presynaptic terminal. There, they may bind with a receptor in the dendrites (post synaptic terminal) of another cell. These receptors are transmembrane proteins. A transmembrane protein is a protein subunit in which the polypeptide chain is exposed on both sides of the membrane. These proteins have active sites where the neurotransmitter binds, and only one neurotransmitter can bind at each receptor. However, other molecules can bind to a receptor. An example of this is how sumatriptan binds to 5HT1b and 5HT1d receptors, or how nicotine binds to acetylcholine receptors. The type of receptor determines the effect of the particular neurotransmitter. This can be to inhibit, excite, or have no effect on the neuron. For example, if the receptor is an ion channel, such as a calcium channel, then the effect will be that the channel is opened or closed. When a Neurotransmitter binds to the receptor, there can be three types of effects 1. Ionotropic (primary messenger) 2. Metabotropic (secondary messenger) 3. Neuromodulation Ionotropic Effects When a neurotransmitter binds to a receptor, it opens the receptor's ion channel. Ion channels are large integral membrane proteins that form pores through the plasma membrane that allow ions to cross. Ions always flow down their electrochemical gradient through channels (passive transport). The core of the pore is hydrophilic, and contains a part of the protein which recognizes only certain ions and allows them to pass through. This is called the selectivity filter. Channels are named by what ion(s) they allow to pass: calcium channel, potassium channel, sodium channel, chloride channel, etc. Another part of the channel is the gate. Only when the gate is open can the ions recognized by the selectivity filter pass through the channel. Gates open in response to a variety of stimuli, including changes in membrane potential or the presence of certain chemicals outside or inside the cell. Channel names often include an indication of what controls the gate: e.g., "voltage-gated calcium channel." There are more than 50 types of ion channels identified now. Metabotropic Effects-Sometimes called secondary-messenger transmission. Lithium acts on this secondary messenger transmission When a neurotransmitter binds to a metabotropic receptor it attaches to a part of the receptor exposed to the synaptic cleft. This activates a tail of the protein inside the postsynaptic neuron. The tail binds to and activates a G-protein inside the cell, and, in turn, the G-protein activates secondary messengers inside the cell. Secondary messengers cause changes in other parts of the cell. The secondary messenger can have a wide range of effects. Some of these effects are: < Open an ion channel < Close an ion channel < Alter the functioning of receptors < Modify production of proteins in the cell < Activate a portion of the cells chromosome Neuromodulation Neuromodulators are similar to neurotransmitters and are released by a neuron like a neurotransmitter. When released they diffuse to nearby neurons and affect all nearby neurons with appropriate receptors. However, they do not affect neurons directly, instead they modulate the effect of neurotransmitters by prolonging or shortening the effect of a neurotransmitter, or by limiting neurotransmitter release by presynaptic neurons. Inactivation / Reuptake of Neurotransmitters After a receptor sets a neurotransmitter free, four phenomenon can occur. 1. Some neurotransmitters are broken down by enzymes, then the pieces return to the presynaptic neuron. There, the presynaptic neuron re-synthesizes the pieces into neurotransmitters. An example of this is how the enzyme called acetylcholinesterase breaks acetylcholine down into acetate and choline. Excessive neuron activity (realized action potentials) can deplete the supply of some neurotransmitters when synthesis lags behind. 2. Glial cells - astrocytes - bind to and remove neurotransmitters from the synaptic cleft 3. Reuptake - some neurotransmitters are absorbed intact by the presynaptic neuron. This is a common way the action of norepinephrine, dopamine and serotonin is stopped. 4. The neurotransmitter diffuses out of the synaptic cleft. PFDANs -Curtis |
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