so let's examine mechanistically how smooth muscle contraction is initiated how you progress through that contraction from a molecular standpoint and how ultimately relaxation occurs in smooth muscle so we've established in the previous video that there is no neuromuscular junction neurons can cause contraction in smooth muscle so can hormones stretch there are many different uh mechanisms that are in play that are specific to one smooth muscle in one location of the body versus another so we're going to generally just say that some stimulus is going to occur and what this stimulus does is it's going to impact a calcium channel this could be a chemically gated channel it could be a mechanically gated channel is just a calcium channel so this stimulus will cause the influx of extracellular calcium so there's an influx of extracellular calcium now for the next part this is just extra information and you're not held responsible for this and i'll just kind of write it in red and i'll put a little asterisk here but it is a cool little process that i want to share with you this calcium is going to activate an enzyme called phospho light base c and phospholipase and i'm just going to abbreviate that as plc phospholipase will take some specific phospholipids not all of them but some specific ones and it'll break it into two molecules the first of which is inositol triphosphate and the second is diacylglyceride or dag both of these molecules are important secondary messengers all that means is there important cell signal molecules on the inside of the cell they're going to cause some sort of response we're going to focus on ip3 so that part you don't need to know now you do need to know this so we have our sarcoplasmic reticulum it's less branchy as it was in the skeletal muscle and we're not dealing with dhp but instead we have a chemically gated calcium channel in the sr and remember the sr is storing vast amounts of calcium ions now the specific chemical that causes this calcium channel to open is actually ip3 so it is an ip3 mediated calcium channel so when ip3 is around and it binds to the channel so let's draw it like so so here's ip3 the channel is open and you're going to have an influx of calcium from the sr into the cytosol now in the skeletal muscle that calcium would have eventually bound to troponin to initiate the power stroke but we don't have troponin in smooth muscle instead there's a different calcium binding protein the name of this calcium binding protein is calmodulin and i'm going to abbreviate calmodulin as cam okay so when calcium binds to cam you have a cam calcium [Music] complex which can now activate a specific enzyme and the name of this enzyme is the myosin light chain kinase or mlck so now is a good time to review the structure of myosin now we've learned that myosin has an actin binding site this is what allows myosin to interact with actin to form a strong cross bridge myosin also has an atp ace domain so this is what the myosin uses to bind to atp and hydrolyze the atp to adp and the phosphate during the power stroke okay so the myosin found in smooth muscle is no different you have the active you have the actin binding domain you have the atp ace domain but there's a third area and we'll just call it sort of the activation site and what happens in the activation site at rest nothing is bound but when you want to initiate contraction mlck a kinase kinases add phosphate groups so basically pis onto other proteins so mlck to that binding site it will add a phosphate group so you have your binding site for actin you have your atpase domain and now in this activation site mlck has put a phosphate group okay so the placement of this phosphate group onto the myosin head and the light chain makes up some of that uh phosphate some of that myosin head so the placement of the phosphate is what initiates the power stroke and as long as that phosphate group is in that activation site the myosin head will move will rotate so you have the power stroke so like skeletal muscle calcium has initiated this mechanical event but unlike skeletal muscle you had extracellular calcium that triggered intracellular calcium release so we're going to just abbreviate that as ci cr for calcium induced calcium release so some sort of extracellular stimulus stimulates the influx of extracellular calcium and that triggers intracellular calcium release okay so the sequence of events stimulus triggers extracellular calcium influx which in turn triggers intracellular calcium release of course from the sr that calcium binds to calmodulin activates myosin like chain kinase which in turn activates the myosin and you have the power stroke so it stands to reason that to relax the sequence of events has to be somewhat in reverse you have to ultimately get rid of calcium okay so how do we remove the removal of cytosolic calcium okay everything boils down to calcium calcium triggered contract contraction the removal of calcium will trigger relaxation now in skeletal muscle you had a calcium pump or calcium atpase that was found in the sarcoplasmic reticulum smooth muscle has that as well but additionally this same protein appears in the plasma membrane as well so while the sarcoplasmic reticulum calcium atpase moves calcium from the cytosol into the sr the calcium atpase and the plasma membrane moves some calcium from the cytosol to the interstitial fluid smooth muscle also has a third way and it uses an antiporter so it's going to use the power of the sodium gradient allowing for the influx of sodium to power the removal of calcium of its concentration gradient so we're going to call this the sodium calcium anti-porter so this again moves calcium from the cytosol to the interstitial fluid so this reduces cytosolic calcium so then what are the sequence of events that occur after that well as calcium levels drop you reduce the calcium calmodulin complex well if you no longer have the calcium calmodulin complex you can no longer activate mlck well if you can no longer activate mlck you can no longer turn on via phosphorylation or via putting that phosphate onto the activation site the myosin okay but how do we remove the phosphate we're just not putting it on anymore but it's already on well luckily there's an enzyme to do this right if an enzyme put a phosphate group onto the myosin there's an enzyme that removes it so there's an enzyme called myosin light chain phosphatase phosphotase or mlcp so this removes the phosphate from the activation site this is always active but at low levels so it's sort of a game of cat and mouse when you are at rest the only enzyme that's active is mlcp so it removes all the phosphate from myosin it's not active but when you have some sort of stimulus to initiate contraction and mlck is active you put the phosphate group on pretty quickly so yeah phosphatase might remove the phosphate but then the kinase slaps it back on and so the myosin has the phosphate on it more than it doesn't so it continues through the power stroke so make sure you understand this sequence of events that begin with the removal of calcium from the cytosol that then cascades into the inactivation of mlck and the end of the power stroke because we're not putting phosphate groups back on that the myosin light chain phosphatase is removing so you can see that this method would kind of protract the time it takes to relax a smooth muscle this is why we get a much more sustained contraction and relaxation that we viewed over here in smooth muscle as opposed to skeletal so we're protracting the time it takes to relax this smooth muscle