Compare and contrast signalling through ionotropic and metabotropic neurotransmitter receptors. Give examples to illustrate your answer. PDF

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This is an essay style answer for the 2016/17 year exam question: Compare and contrast signalling through ionotropic and metabotropic neurotransmitter receptors. Give examples to illustrate your answer. including relevant diagrams ...

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Q. Compare and contrast signalling through ionotropic and metabotropic neurotransmitter receptors. Give examples to illustrate your answer. There are two families of receptors associated with the opening and closing of ion channels, both of which do so in very different ways. These are ionotropic and metabotropic receptors. Ionotropic receptors are made up of about 4/5 protein subunits, meaning that they are referred to as multimers. Each of these individual protein subunits contribute to the pore of the ion channel. The ionotropic receptor is divided into two functional domains. The first is the extracellular site, this site binds the signal molecules, such as neurotransmitters. The second domain is the membrane spanning domain, this forms the ion channel into the cell. When a ligand, i.e. a neurotransmitter, binds to an ionotropic receptor at the extracellular domain, the channel is then activated, allowing the flow of ions through. Ionotropic receptors generally mediate rapid post synaptic effects. The post synaptic potentials arise within a millisecond or two of an action potential invading the presynaptic terminal and only lasts for a few tenths of a millisecond or less. The second family of neuroreceptors that we will discuss are the metabotropic receptors. These receptors rely on one or more steps to result in the eventual move of ions through a channel, giving rise to the metabotropic name. Metabotropic do not have their own ion channels. They function to affect the opening and closing of other channels through the use of intermediate molecules. These intermediate molecules are called G-proteins. As the metabotropic receptors work in conjunction with G-proteins, they are referred to as G-protein coupled receptors (GPCRs). Like, ionotropic receptors, metabotropic receptors also have two domains, one of which is an extracellular domain which binds ligands such as neurotransmitters, whilst the intracellular, transmembrane domain binds the G-protein inside the cell. A typical G-protein has three subunits α, β, and γ. The alpha subunit binds to guanine nucleotides, either GDT or GTP. When GDP is bound to the alpha subunit, allows the subunit to bind to beta and gamma subunits, forming an inactive trimer. When an extracellular signal binds to the receptor, it activates the metabotropic receptor, causing GDP to be replaced with GTP on the alpha subunit of the G-protein. When GTP binds, the G-protein becomes activated and the alpha subunit dissociates from the beta complex. Once activated, the GTPbound alpha subunit, and the beta complex are capable of binding downstream effector molecules that mediate a variety of responses in the target cell, for example, the G-protein may interact directly with ion channels, causing the channels to open or close. Activated Gproteins may also bind to other effector proteins such as enzymes that make intracellular messengers that mediate a variety of responses in the target cell An example of one such receptor is the β-adenoreceptor, a metabotropic receptor involved in the fight or flight response in humans

Metabotropic receptors typically produce much slower responses thn ionotropic receptors when activated. Reaction times may range from hundreds of milliseconds to possibly minutes, or sometimes even longer. Some transmitters are capable of activating both ionotropic and metabotropic receptors, resulting in the production of both fast and slow post synaptic potentials at the same synapse....