Muscle Contraction Flashcards
How is skeletal muscle structured?
The skeletal muscle is attached to bones.
Very long cells- up to 30cm
Many nuclei because they are formed from myoblasts coming together at development
Have this distinctive striped pattern because the proteins involved in muscle shortening are arranged in an organised pattern
How is cardiac muscle structured?
The cardiac muscle is very similar inn appearance to the skeletal muscle
Found in the heart
Same striped appearance due to the contractile proteins (myofilaments)
Only have a single nuclei
Far shorter than skeletal muscle cells- only 100 microns
Have a branched pattern
How is smooth muscle structured?
Smooth muscle called so because these muscle cells do not have a striped patter because its contractile proteins are not arranged in a logical pattern
Involved in all the physiological processes that we don’t think about for example in the:
Arteries
Guts
Bladder
Reproductive organs
What is contraction?
Contraction is the interaction of actin and myosin
Fuelled by ATP
Driven by a rise in [Ca2+]
What are the two types of filaments? What are the structures within them?
There are two types of filament:
The thin, composed mainly of actin
And the thick, composed mainly of myosin
The actin shown in green are circling the internal myosin molecules shown in red
The stripy pattern comes about because of regions, the I band, where there’s only actin
There are regions, the A band, where there’s only myosin
And then you have regions where there’s an overlap
The gap between the two Z discs is called the sarcomere- this is the functional unit
The sarcoplasmic reticulum is very important, it is intimately arranged along the myofibril along the contractile proteins
The sarcoplasmic reticulum is a complex convoluted store of calcium
How are the thin and thick filaments structured?
Ok so here is the thin filament and here is the Z disc formed from alpha actinin (kind of like a scaffolding protein)
And the thin filament is formed mainly from actin (shown as the red beads) and there are two other protein associated with it:
Troponin which is formed of a calcium binding domain Troponin-C and a tropomyosin binding domain Troponin-T
Tropomyosin which lies along the actin molecule, blocking the active site where myosin would interact
The thick filament is arranged from a number of myosin molecules back to back
The myosin molecules are made up of a long tail and a bulbous head that is connected to the tail by this hinge region of amino acids which allows the myosin head to flex
The myosin head has two important region:
A binding domain that interacts with the active site of actin
An ATPase where ATP is hydrolysed to ADP and phosphate
And that high energy myosin has a different conformational shape than the low energy myosin
So there’s this movement involved that is driven by ATP
How does the contraction motion occur?
The actin is pulled across the myosin via the myosin head into the centre of the sarcolemma
So what we have is a cycle of attachment, movement and detachment
Binding- myosin cross bridge binds to actin molecule
Power stroke- cross bridge bends, pulling thin myofilament inwards
Detachment- cross bridge detaches at end of power stroke and returns to original conformation
Binding- cross bridge binds to more distal actin molecule; cycle repeated
How does calcium contribute to contraction?
When calcium concentration goes up, this binds to troponin and troponin then binds to tropomyosin and pulls the tropomyosin out of the way allowing myosin and actin to interact
How is the T tubule system attached to the myofibrils?
These invaginations of the sarcolemma from the exterior deep into the cell- these are called transverse tubules or the T tubule system
These T tubules, proteins shown in purple, become closely associated with the sarcoplasmic reticulum, the calcium store, that is surrounding the contractile proteins
What happens earn a skeletal muscle is stimulated by acetylcholine?
What happens when a skeletal muscle is stimulated by the acetylcholine released from motor nerves is that it binds to its receptor, which causes depolarisation and if sufficient opens up sodium channels
Then you get a wave of depolarisation passing down this T tubule system and deep into the cell
Within these tubules, are these proteins known as dihydropyridine proteins (DHPs) that are physically interacting with a calcium release channel in the sarcoplasmic reticulum
This calcium release channel is known as the ryanodine receptor (Ryr)
When the cell is stimulated the dihydropyridine receptor changes conformation, cause its voltage sensitive and this alters the calcium release channel causing calcium to be released and contraction to occur
How does stimulation of cardiac muscle differ (from skeletal)?
The situation is very similar in cardiac muscle but now we don’t have a physical interaction between the voltage sensor and the calcium release channels
You have a very similar protein to the dihydropyridine receptor which is actually a calcium channel
So now you get the stimulation of the T tubule system, activation of this voltage sensitive ion channel, and it is the influx of calcium that then causes calcium to be released from the sarcoplasmic reticulum in a process that’s known as Calcium Induced Calcium Release (CICR)
How are smooth muscles structured differently?
1.Smooth muscle is very different from the other two types of cells
First of all there is no t-tubules and the myofilaments (contractile proteins) are not arranged logically
So as the smooth muscle cells contract they don’t shorten but rather ring out like a tea towel
2.There’s a second difference between smooth muscle and the other two types of striated cells which is the nature of the calcium sensor
Here we have calcium binding to troponin in skeletal and cardiac muscle cells
In the smooth muscle cells it binds to calmodulin
3.In smooth muscle there’s no troponin or tropomyosin around there are some other regulated proteins
The myosin is a very different isoform to that found in skeletal muscle:
It has a low ATPase activity
It has a lower affinity for ATP
It is rather structurally puny
How does smooth muscle contract?
You can get a rise in calcium through a number of different mechanisms
1.So this can be receptor mediated release of calcium from an intracellular calcium store but in this case its from the production of a diffusible messenger called inositol trisphosphate
2.Its made from a membrane phospholipid, broken down through a number of enzyme steps and then this releases calcium
3.At the same time you can get massive calcium influx through voltage-gated calcium channels which are very similar to those found in the t-tubules of cardiac muscle cells
4.This rise in calcium leads to contraction
What happens is that the rise in calcium binds to calmodulin and it stimulates myosin light chain kinase
5.A kinase puts a phosphate on a serine or threonine, in this case its serine 19 of the myosin light chain
6.This increases ATPase activity of the myosin head ~1000 fold and makes the myosin a lot more structurally rigid