Signal Amplification & Dissemination

00:01 What are the steps in getting that signal once it’s bound to the ligand to do something useful or do a physiological response? We have a number of steps in this signaling process.

00:15 We’re going to break them into six different steps.

00:20 The first step is recognition.

00:23 You need to make sure that the ligand binds to the receptor.

00:28 So recognition is not only the first step here, but it is so important if you don’t have this response, you’re not going to get any of the other steps.

00:39 What is that recognition? The ligand has a specific, usually, confirmation.

00:47 It has a certain charge.

00:49 It has a certain way in which it’s going to bind in a particular receptor binding pocket.

00:56 Oftentimes, it is very specific to the ligand itself or class of ligands.

01:04 And so, they might have to be one type or a family to bind to a particular receptor.

01:11 We oftentimes talk about that in terms of its affinity for a receptor.

01:18 Certain ligands have high affinities and other ligands have lower affinities.

01:24 It’s important to understand that reaction to know what recognition is going to look like.

01:31 Not only do you have to have the right ligand and the right receptor, you’re going to have to move that information from the cell surface into the cell.

01:42 How do you do that? That’s in a stage that we oftentimes call transduction.

01:48 So in a G protein-coupled receptor, using this as an example, you might activate a G protein to help transduce that signal into something more useful.

02:02 So it is the receptor causing the change in either the proteins around it or activating a molecule around it to start that response.

02:16 Transmission is getting that transduced signal to the right spot.

02:22 So it might involve activating an enzyme so that then there can be signaling of the right target proteins.

02:32 Once you have the right target proteins activated, then you get an effect.

02:38 And this is what you want to have happen, right? You want to either have proteins being made, enzymes being activated, genes being up regulated, you might have proteins being built to sit in the cytosol or other cell proteins that might have interesting activities.

02:57 But to get to this important effect, you have recognition, transduction, and transmission.

03:06 Once you’ve made this new protein or done this kind of effect, you get a response.

03:12 Now, the response is what we were usually concerned with in physiology.

03:17 So once you’ve made a transport protein, how does it affect transport? Once you’ve activated this enzyme, how has it changed the function of the cell? Once you’ve up regulated this gene product, what happens to not only its expression but downstream of that? Interesting though, once you have these interesting effects that happen, you’re going to have to eventually turn the whole process off.

03:47 So, you’re going to be have to be able to terminate this particular cell signaling.

03:51 If you don’t terminate the cell signaling, it will keep going and going and going.

03:56 And so, even though you wanted to amplify the signal initially, eventually, you have to turn it off.

04:02 How do you turn it off? Well, you could either remove the ligand or block it at some point.

04:10 And different cells and different receptor interactions will utilize a different process in activating or terminating the cell signaling.

04:20 But you’ll notice that you’ll have these six steps in almost all cell-to-cell signaling interactions.

04:28 Let’s go through a specific example though rather than just dealing with this on a theoretical level.

04:38 So if we have an acetylcholine nerve, so this is a nerve that releases acetylcholine, it is sent from a neural packet or quanta of information, so releases from the presynaptic nerve acetylcholine, traveling across to the receptor on the postsynaptic membrane.

05:03 Acetylcholine will only bind to a receptor that recognizes it, right? The type of receptor that’s going to recognize it is muscarinic receptor.

05:13 So acetylcholine has two different types of receptors, nicotinic and muscarinic.

05:19 But if you have a muscarinic receptor recognizing that acetylcholine being released, that’s our first step, is recognition.

05:29 The second step is once the receptor is activated, it needs to do something.

05:34 A muscarinic receptor is a G protein-coupled receptor.

05:39 The G protein-coupled receptors have these little G proteins around the base of the receptor.

05:47 There are three different types of G proteins around this receptor.

05:53 The gamma and beta components can then cleave off and signal something else.

06:01 In this case, they’re transmitting that signal to somewhere and that part is a potassium channel.

06:10 That potassium channel will then be activated.

06:13 If you activate a potassium channel, you open it up using the gradient between the inside the cell and outside the cell, potassium will leave the cell, and that is the effector, is the potassium channel.

06:31 The response is a hyperpolarization of the cell.

06:36 That hyperpolarization, if it’s something like in a heart cell around an SA node, will slow heartrate.

06:44 So these are the responses that you get.

06:48 You can’t have this response go on forever, though.

06:51 Eventually, you’re going to have to terminate it.

06:54 So how does a muscarinic receptor terminate the response? There is an enzyme that is in the presynaptic membrane that will break down acetylcholine.

07:07 It’s called acetylcholinesterase.

07:09 Acetylcholinesterase will break down acetylcholine into inactive products, so then it can no longer bind to muscarinic receptors.