The Cholinergic Receptors

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• published: 27 Nov 2014
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Understand the cholinergic receptors once and for all! The Cholinergic Receptors. This is a high-yield topic. You really need to understand this when you're going into your boards or exams. These receptors are found in the central and peripheral nervous systems, and they use Acetylcholine as their neurotransmitter. Thus, they can also be referred to as Acetylcholine Receptors, and their abbreviation is ACh for Acetylcholine and R for Receptor. There are two main types of these Cholinergic Receptors: the Nicotinic Acetylcholine Receptors and the Muscarinic Acetylcholine Receptors. The Nicotinic Acetylcholine Receptors are named such because they are responsive to both Acetylcholine and Nicotine. They are ionotropic receptors, meaning that they are ligand-gated ion channels. When stimulated by their neurotransmitter, they themselves become an ion channel. The Muscarinic Acetylcholine Receptors, on the other hand, are named such because they are responsive to Acetylcholine and Muscarine. They are a different kind of receptor. They're what's called a Metabotropic Receptor, meaning that they act through a second messenger system, which in this case refers to the fact that they are G protein-coupled receptors. Let's talk about the Nicotinic Cholinergic Receptors first, and this is abbreviated the same as what we've seen, AChR, except now with an "n" in front of it to denote Nicotine. So the Nicotinic Cholinergic Receptors, they're directly linked to ion gated channels, as I previously said. There is no second messenger system here. The receptor is a physical part of the ion channel. These ion channels are made of five subunits, and they're arranged symmetrically around a central pore through which ions travel when opened. Also, each of these five subunits is made of four domains, which we might talk about later. However, it's not necessarily high-yield right now. When stimulated by either Acetylcholine or, remember, these are Nicotinic Cholinergic Receptors, so either Acetylcholine or Nicotine can stimulate them, there is an initial stimulation, an initial opening, followed by a blockage or a refractory period. This is important and interesting to talk about because it's related to how some of the drugs work that we will talk about in other lectures. Let me give you a quick visual example of what is happening when these receptors are stimulated. I am going to place two molecules of Acetylcholine on the screen and then two separate ions, and these ions can be Sodium, Potassium, Calcium, and so forth. So what is going to happen is that the Acetylcholine molecules are going to come down and interact with the receptor/ion channel. This is going to cause a conformational change in the shape of the ion channel, which is going to open the central pore to allow ions through. Let's take a look. Kind of interesting, isn't it? Let me repeat this a couple of more times. Kind of neat how that works, huh? Well, as if we didn't have enough abbreviations to remember, I have to add two more, unfortunately. There are two sub-types of the Nicotinic Acetylcholine Receptors: the Neuronal-type, abbreviated Nn, and the Muscle-type, abbreviated Nm. The Neuronal-type is found in both the central and peripheral nervous system, and it is most often found "Up-Stream" in the nervous system, from other receptor types. So take for example the sympathetic nervous system and the associated Adrenergic Receptors. For a sig to get through to the Adrenergic Receptors, it must first travel through a Neuronal-type Nicotinic Receptor in an "Up-Stream" ganglion or nerve. The Muscle-type Nicotinic Receptors are found post synaptically in the Neuromuscular Junctions, and they are responsible for our skeletal muscle contraction. They are what let us move and breathe consciously. So keep these two subtypes in mind. At the end of this lecture, I will give a picture and an example and walk you through where they are. But for now, let's skip on to the Muscarinic Receptors. Okay, so the Muscarinic Receptors are a little bit different than the Nicotinic Receptors. First of all, they're named Muscarinic Receptors because they are responsive to Acetylcholine and Muscarine. Also, they use a second messenger system to propagate the signal. In this case, it's the G protein-coupled receptors. I am not going to go into great detail on the G protein-coupled receptors. There will be a separate lecture for that. However, just as an overview, let me walk through what's happening. This picture on the right represents six basic steps of a G protein-coupled receptor. Let's zoom in on step one. Okay, what we have here is the receptor within the membrane of the cell. The brown oval near the top represents the ligand. In this case, we're talking about Acetylcholine or Muscarine. The ligand binds to the receptor and induces a conformational change. This conformational change activates the alpha sub unit, which then exchanges its GDP for GTP.