New Chapt 12-Biochem of synaptic trans(1)

New Chapt 12-Biochem of synaptic trans(1) - CHAPTER 10...

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121 CHAPTER 10 BIOCHEMISTRY OF SYNAPTIC TRANSMISSION The main tenet of the vesicle hypothesis is that the transmitter is stored in vesicles and the contents of the vesicles are released when these vesicles fuse with the terminal membrane. The issues we address in this chapter concern how and where the neurotransmitters in the axon terminal are synthesized and how the transmitters, once released from the axon terminal, are recycled so they can be used again. The general theme is as follows. The vesicles themselves and the enzymes required to synthesize the neurotransmitters are made in the cell body, which contains almost all the protein synthetic machinery of neurons, and is in essence, the manufacturing center of the neuron. The “things” (vesicles, mitochondria, enzymes, etc) made in the cell body are then transported to the axon terminal through a process called axoplasmic transport. The axon is chock full of cytoskeletal elements, microtubules and microfilaments, which form what is in essence a railway system. Fig. 1. Basic features of synaptic transmission. Organelles, such as vesicles, and enzymes are transported from the cell body to the terminal via cytoskeletal elements, shown as vertical lines in the axon. Transmitter released from vesicle binds to ACh receptors in post-synaptic cell and open ion channels. The ACh is then hydrolyzed (not shown) and one of the products is then transported back into the cell by a transporter. The product is then transported into empty vesicles in the cell, and the vesicle can be recycled. Complex proteins called molecular motors, bind these organelles and enzymes and the molecular motors attach themselves to this railway system. Powered by the hydrolysis of ATP, these molecular motors actually move along the microtubules and carry their cargoes from the cell body to the axon terminal. This is what is meant by axoplasmic transport. Once in the axon, the enzymes act to synthesize the neurotransmitters from chemicals that are already in the axon. Those chemicals either are manufactured in the mitochrondria present in the terminal, or are transported into the axon from the extracellular space in ways that are described below. How the neurotransmitters are synthesized and
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122 packaged in the vesicles is one of the main themes of this chapter. Once an action potential invades the axon terminal, it causes the release of the neurotransmitter contained in the vesicles into the synaptic cleft, where the transmitter binds to special receptors on the post-synaptic cell. The binding is non- covalent and is regulated by the laws of mass action. That is, the greater the concentration of transmitter in the cleft, the greater the amount of binding onto post-synaptic receptors, and when the concentration of transmitter in the cleft declines, the transmitter disassociates from the receptors and diffuses into the cleft. Since the actions of transmitters must be brief, the presynaptic cells have a variety of ways for “clearing”,
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This note was uploaded on 09/19/2011 for the course BIO 365R taught by Professor Draper during the Spring '08 term at University of Texas.

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New Chapt 12-Biochem of synaptic trans(1) - CHAPTER 10...

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