钙对肌球蛋白的运作机制

I'm gonna draw for you the heart and we're gonna actually do a little bit of zooming in now taking a look at exactly what happens both in the wall of the heart but also going even further in so let's start with the heart wall whoa what would you see if you were to kind of zoom in you might see heart cells and this is kind of a hard sell with some branches here and you remember a heart cell besides just having branches to kind of make it very distinct looking it has sometimes one but also sometimes two nuclei now let's say we were to zoom in again on this heart cell what would we see if we we kind of went further well you know that there are lots and lots and lots of proteins inside that heart cell and the ones we usually have been concerning ourselves with are the actin and myosin these are the kind of classic cell proteins that allow it to contract so it might look a little bit like this right with her our Acton's kind of spaced out a little bit from each other I'll label it as I go this is our actin and in the middle of the actin you've got myosin right so you've got this purple myosin and it looks maybe something like this with little myosin heads hanging off of it and you've got some on both sides and these myosins are going to be tethered to the wall right this this wall at the end and I'll draw that tethering with green this might be something like that and this is basically known as Titan this protein Titan is what kind of keeps the myosin from from drifting away you could think of it as well what happens over time is that these myosins and actins are gonna start binding right they're gonna start binding to one another and we call these actin myosin cross bridges or you might hear different terms but basically the two are interacting with each other and what the myosin is gonna want to do is it's gonna want to yank this way right it's gonna want to bind to the actin like this and yank it that way and in fact all these little myosins are gonna kind of act the same way they're gonna want to yank the actin in the same direction and on the opposite side you've got pulling in the opposite way right you've got pulling towards the middle basically so if this was to work what would happen well at the edges here these things right here we call these z-disks z-disc you might have heard the term z line because it looks like a line under microscope but if you actually kind of zoom in and you you could you know go up close to it it's basically a disk of protein right so these the Z disks if if our actins and myosins are indeed kind of interacting and tugging on one another the way that we think they should these are going to be pulled inwards right this is almost like kind of bringing a wall in towards the center you can kind of think of it that way and you can kind of think of the actin is like a rope hanging off of this z disk and the myosin is literally kind of hands-on grabbing the rope and yanking on the disk and in fact lots and lots of myosin heads are doing it all at once kind of in unison so that's why these disks get moved towards the center and when they get moved towards the center we literally call that contraction of the cell or cell contraction and so these actin ropes if you want to keep thinking them that way are going to of course they're not gonna get cut or shrunk or anything they're gonna be the same length but the Z disks yet brought closer together so overall the effect is that the entire thing looks a little bit more crowded because the myosin has kind of brought everything to the center so that's cell contraction now I'm gonna actually take a little further zoom in let's say you actually wanted to zoom in I mean let's look at two of these let's say you wanted to zoom in to something like this this white box here and kind of take a look at what that might look like let's see that I'm gonna make a little bit of space on my canvas but let's just keep that scene like that let me start by drawing the actin it'll look something like this and I'm gonna try to keep it somewhat consistent so you can actually see what it is that we're gonna try to draw along the way so we've got our actin and we've got our myosin and our myosin I'm gonna warn you kind of in the same direction as orange in the other pictures something like this let's say it's one head there and let's save got our second head right there right so you've got our myosin and of course our myosin is going to continue in really in both directions but but really it's the majority the myosin is going to be that way right so we've got our actin we've got our myosin and the story from the previous picture kind of ends there but we know that we've got our myosin actin by binding sites are gonna be kind of bound up by Tropo myosin right tropomyosin is kind of snaking its way through looks a little bit like that right and it's gonna basically sitting in all of the binding sites that myosin really can't get in there and in fact there's also another protein we talked about the fact that there's a protein called troponin and troponin is also kind of in the same area I'm actually gonna draw troponin like this you might be thinking why am i drawing troponin in three parts why is there you know a little crescent-shaped thing and then also two little circles and actually troponin even though before previously we talked about troponin kind of as one protein this whole thing is probably more commonly known as troponin complex instead of just the one word troponin it's actually a complex of proteins and there are three to be precise there's troponin C over here I and T and in fact if that's not clear let me put it on this side right here so you can see it so this troponin C troponin I entrepot ninh T and in yellow we've got our tropomyosin so now our picture is looking a little bit more accurate right we've got all this stuff going on with the tropomyosin getting in the way of our myosin head now what's gonna make that troponin complex move away what's going to kind of clear space for our myosin head well we know that it's going to be calcium and I'm gonna draw calcium here binding to which part of the troponin complex well troponin see see like calcium is what's gonna bind the calcium so troponin C is gonna bind calcium and once it does once the calcium is bound there it then can scooch the trip hope the tropomyosin out of the way so now the tropomyosin I'm gonna just draw with some green arrows is gonna basically be scrooched out of the way and the myosin head is very happy because it can bind finally to the actin now if there's no calcium like you can see in our friend to the right this troponin sorry this troponin is not going to bind to the calcium so the tropomyosin is not moved out of the way it's in the way and at the end of the day the myosin is gonna be sad because it cannot bind to that actin so you can see now the the myosin from a myosin standpoint it likes when calcium is around because that means it can do work now let me clear a little bit more space for us and I'm gonna bring up one final point I mean if we think that a happy myosin head is a working myosin head if we take that approach it's a little bit like I guess getting a job right yeah it makes everyone happy when they have a job when they're employed and myosin heads are no different they want to be employed and so how do you employ a myosin heads how do you get more jobs for myosin heads well there are basically two strategies for increasing what we call inotropy ER basically getting more myosin heads working so two strategies let's go through them one by one so the first strategy would be what well you could affect the amount of calcium right you could get more calcium around that would be one strategy and the other strategy might be you could have the troponin C remember the troponin C is part of the complex that's actually binding the calcium you could get troponin C to be more sensitive to calcium more I'm going to put that in quotes because what I mean by sensitive well essentially you're saying that troponin C could change its shape or its conformation to bind the calcium that is already around more easily so basically bind calcium more easily but I wanted to put the word sensitive cuz sometimes you'll you'll see that word and you wonder what it means so buying calcium more easily so these are the two basic strategies and you can imagine you could imagine you know increasing in one strategy increasing the calcium but leaving the sensitivity of troponin see the same really not changing how easily it will bind calcium and the overall effect is more myosin heads are working so more myosin heads are working that would be the the kind of overall effect right and you could flip it around you could say well maybe maybe you have the same amount of calcium maybe you don't actually increase the calcium but you do make troponin C bind the calcium that is there more readily or more easily well in that situation you also get more myosin heads working right so in either scenario in either strategy you're going to get more myosin heads working and so these are the two basic strategies for inotropy