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"Why so many receptors?" A receptor is a protein found on the cell surface membrane which transduces a signal once a molecule binds to it. In the case of synaptic transmission the nature, magnitude and sign of a neuron's response to a neurotransmitter is determined by the type of receptors present either on the pre or post synaptic membrane. Once the neurotransmitter binds to its receptors the nature of the neuronal response varies as there is either the direct opening of the channel or a change in the concentration of intracellular metabolites. The magnitude of a neuronal response is determined by the number of receptors and the amount of neurotransmitter released. Finally the sign of the neuronal response also varies as it can be either inhibitory or excitatory. There are two main classes of receptors that are involved in synaptic transmission and these are ionotropic receptors and metabotropic receptors. A given neurotransmitter can activate more than one type of neurotransmitter receptor and this allows for diversity of post synaptic responses initiated by one neurotransmitter. In this essay the two classes of receptors will be considered as well as the receptors that are associated with noradrenaline, glutamate and GABA. Ionotropic receptors, also known as ligand gated ion channels, are integral membrane proteins that are formed by a multisubunit complex composed of five individual proteins that combine to form an ion channel through the membrane. These ion channels are largely impermeable to ions in the absence of neurotransmitter. However, when the neurotransmitter binds to the ionotropic receptor it leads to a rapid conformational change in the receptor which triggers the rapid opening of ion channels. This action allows ions to flow down their electrochemical gradients which either result in depolarization (if ionotropic receptor has non selective cation channels) or hyperpolarisation (if ionotropic receptor has chloride ion channels) in the postsynaptic membrane. This mechanism has been proven by experiments such as the patch clamp recording technique which measures small currents flowing through single ionic channel. The use of the patch clamp has shown that the binding of neurotransmitters leads to the opening of ion channels which then generates current. The flow of ions through these receptors is inhibited when the neurotransmitter dissociates from the receptor. Ionotropic receptors control fast synaptic events in the nervous system as the receptors leads to very rapid changes in the postsynaptic membrane potential. It is the speed in which they act that provides the evidence that the receptor and ionic channel are coupled and there are no intermediate biochemical steps involved. The second class of receptors that are involved in synaptic transmission are metabotropic receptors also known as G protein coupled receptors. Like ionotropic receptors these are also intergral membrane plasma proteins. Each metabotropic receptor is formed by a single polypeptide chain which folds to form seven membrane spanning alpha helical segments. The protein also consists of an extracellular N terminus which is glycosylated, a large cytoplasmic loop that is made of hydrophilic amino acids between segment 5 and 6 and a hydrophilic domain at the cytoplasmic C terminus. The cytoplasmic loop between segments 5
and 6 is the key region which interacts with the intracellular G proteins. One of the key differences between ionotropic and metabotropic is that the latter indirectly activates or inactivates ion channels through a series of enzymatic steps. Due to this neurotransmitters that activate metabotropic receptors produce responses that have a slower onset but a longer duration.
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