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| Neurotransmitters and Receptors |
Neurotransmitters are usually small molecules, such as amino acids (e.g, glutamate and aspartate) and amines (e.g., dopamine, serotonin, and histamine). Some neurotransmitters stimulate neurons to fire, while others inhibit firing. The effect of the neurotransmitter comes about by its binding with receptor proteins on the membrane of the postsynaptic neuron. Each neurotransmitter binds specifically in a lock-and-key mechanism to its type of receptor. Neurons in different pathways will often have different types of receptors in a given family. For example, dopamine binds to dopamine receptors, but there are about a dozen subtly different dopamine receptors. Neurobiologists think that the human nervous system uses at least fifty neurotransmitters, but about ten carry out most neurotransmission. Many of these neurotransmitters are highly conserved in other organisms. Most neurons release only one type of neurotransmitter.
Neurotransmitters are released in a process called exocytosis. When the action potential reaches the end of an axon, the depolarization causes calcium channels to open. The calcium causes synaptic vesicles that carry the neurotransmitter to fuse with the cell membrane. This fusion allows the neurotransmitter to be released into the synapse. Although exocytosis occurs in many cell types, neurons use a specialized form in which calcium causes a chain of events that culminates in fusion of the vesicles.
There are two general categories of receptor proteins: ionotropic and metabotropic. Activation of ionotropic receptors causes membrane ion channels to open or close. In contrast, activation of metabotropic receptors involves an intracellular biochemical cascade. Such a cascade may end with the opening or closing of ion channels or other intracellular effects.
As long as the neurotransmitter remains in the synapse, it will continue to bind its receptors and stimulate the postsynaptic neuron. At some point the signal is no longer needed. Moreover, continual stimulation can injure some neurons. So, halting the stimulus is just as important as the appropriate starting of the stimulus. How does the neurotransmitter leave the synapse? There are several ways, such as diffusion away from the synapse or breakdown of the neurotransmitter by specific enzymes. Another common mode, called reuptake, involves specialized molecules present on the membrane of the presynaptic neuron. These molecules, called neurotransmitter transporters, have receptor sites that will bind to the neurotransmitter and actively transport it out of the synapse, back to the presynaptic neuron. That neuron can then reuse the neurotransmitter. The action of several drugs takes place at the reuptake stage.