Excitation Contraction Coupling in Cardiac and Skeletal Muscle Flashcards
What is excitation contraction coupling ?
A process by which there is a conversion of an electrical signal to a mechanical process (contraction of muscle).
Briefly describe what happens at the neuromuscular junction when muscle cells are innervated
Electrical signal propagates down to the axon terminal.
Change in membrane potential opens Ca channels.
Influx of Ca enables synaptic vesicles to fuse with the membrane.
ACh diffuses across the synaptic cleft and binds to nicotinic receptors.
Change in conformation causes them to open.
K+ moves out of the muscle and Na+ moves in.
Influx of Na+ causes depolarisation of the plasma membrane.
Allows threshold potential to be reached and action potential is fired.
Describe the nicotinic receptor
Ligand gated
Change in conformation by ACh binding
Describe depolarisation of the muscle fibre
Propagation of an action potential deep into the tissue through T tubules.
Change in membrane potential, which activates the voltage gated Ca2+ channels, called the DHP receptors.
This activation causes a conformational change of the channel, which allows direct coupling between DHP receptor and type 1 ryanodine receptor.
As the DHP couples with the ryanodine receptor (located in the SR), the ryanodine receptor opens, allowing Ca2+ to flow out of the stores into the cytoplasm.
Concentration of Ca2+ reaches a critical concentration which allows it to bind to troponin C, enabling actin and myosin filaments to slide across each other, causing muscle contraction.
Describe features of skeletal muscle action potential
The action potential is very brief, Na+ flows in causing a rapid depolarisation.
There is a lag between the action potential and a change in tension (onset of response)
State a key difference between cardiac and skeletal muscle action potential
Contraction of skeletal muscle doesn’t overlap with the action potential. There is a lag period.
What is a latent period ?
The time between the peak of action potential to the onset of the contractile response (onset of tension).
Why does a latent period exist ?
As the electrical signal generated from the action potential has to be delivered deep into the tissue fibre.
What is the T tubule system ?
A membrane invagination into the tissue, which allows the depolarisation of the membrane to be delivered into the muscle fibre.
What is the role of transverse tubules in contraction ?
Allows depolarisation of membrane to be delivered deep into the tissue.
What is the function of the sarcoplasmic reticulum ?
The internal calcium store in muscle.
Major Ca2+ store.
What is the role of the terminal cistern in contraction ?
The end regions of the sarcoplasmic reticulum are called the terminal cistern.
They store Ca2+ ions.
What is a key driver of tension ?
An elevation of intracellular calcium concentration.
Calcium binds to troponin C which allows contraction to occur.
Why is there no requirement for extracellular Ca2+ during the activation of contraction ?
The direct coupling between the DHP and ryanodine receptors drives the process of excitation contraction coupling in skeletal muscle.
State the junctional foot proteins involved in mechanism of Ca2+ release
DHP (Dihydropyridine receptor)
- L-type voltage gated calcium channel in the T tubule membrane
Ryanodine receptor
- Calcium release channel in the SR
Describe how junctional foot proteins work
Membrane depolarisation opens the voltage gated Ca2+ channels (DHP receptors)
The conformational change allows direct coupling between DHP and type 1 ryanodine receptors.
Release of calcium from stores, combines to inactivate troponin C leading to muscle contraction.
Briefly describe the release of calcium from stores
At rest, the SR has a high conc of calcium in stores, and when the muscles are relaxed the conc of calcium in the cytoplasm is low.
When the ryanodine receptor is activated, it open and Ca flows down its conc gradient, causing an elevation in cytoplasmic Ca conc.
Describe cytoplasmic calcium concentration values following depolarisation
Increases form <10^-7 M to >10^-5 M
What is nifedipine ?
A voltage-gated Ca2+ channel blocking drug, used to treat (smooth muscle) hypertension, migraine and atherosclerosis.
Acts on DHP receptors
What is dantrolene ?
A spasmolytic drug acting as a skeletal muscle RELAXANT. Used to treat (sarcoplasmic reticulum) muscle spasm and malignant hypothermia.
Acts on type 1 ryanodine receptors.
What is a cause of malignant hypothermia ?
Mutation that codes for the ryanodine type 1 receptor.
How can you get skeletal muscle relaxation ?
If you lower the amount of calcium, you’ll get relaxation.
In skeletal muscle, the main driver of calcium reduction in the cytoplasm is a calcium ATPase called SERCA.
SERCA
Sarcoplasmic Endoplasmic Reticulum Calcium ATPase
- A calcium pump in the SR membrane
What does SERCA require to function ?
ATP is required in order to activate the pump.
How does SERCA work ?
An increase in intracellular calcium concentration activates SERCA
Active transport of calcium from the cytoplasm into the SR.
2 calcium ions per molecule of ATP hydrolysed
How many calcium ions are pumped back into stores per molecule of ATP hydrolysed ?
For every molecule of ATP that is hydrolysed, 2 molecules of calcium are pumped back into the store.
This is quite a high energy process.
Describe cytoplasmic calcium concentration values during relaxation
[Ca2+] decreases to <10^-7
What is calsequestrin ?
A calcium binding protein
Binds 43 Ca2+ ions per molecule
Role of calsequestrin
Stores calcium at high concentrations in the terminal cisterna to establish a concentration gradient from the SR to the cytoplasm.
Describe pacemaker cells
Specialised muscle cells
Unstable resting potential
Undergo automatic rhythmical depolarisation
State a difference between skeletal and cardiac muscle contraction
Skeletal muscle needs to be innervated for it to contract, however cardiac muscle doesn’t need to be innervated.
The heart can generate its own rhythm by specialised cells in the SA node called pacemaker cells.
What can the rhythm of the heart be controlled by ?
Autonomic innervation
Describe function of acetyl choline
Neurotransmitter that slows rate
Innervation is localised to pacemakers
Describe function of nor-adrenaline
Neurotransmitter that increases rate and strength of contraction
Innervation by diffusion
What is the key driver of contraction in cardiac muscle ?
Calcium
Conversion of electrical signal into a mechanical process.
Describe the action potential in cardiac muscle
Action potential is much longer than skeletal muscle
Fast conducting tissue <– fast depolarisation driven by sodium channels
Describe cardiac muscle tension response
A change in tension occurs DURING the action potential
Depolarisation of the plasma membrane activates voltage gated calcium channels
Influx of calcium through channels binds to type 2 ryanodine receptors in cardiac muscle.
This drives the release of calcium.
As calcium is influxing into the cell, this prolongs the action potential so you get contraction during firing of action potential.
Explain calcium induced calcium release
25% of the required calcium enters through the L-type (DHP) calcium channels
This calcium binds to the type 2 ryanodine receptors in the SR.
Binding of calcium induces the release of calcium.
75% of calcium enters through calcium sensitive calcium release RYR protein in the SR>
Describe how the membrane potential is reset
Sodium/Potassium ATPase, where sodium gets pumped out and potassium gets pumped in, which resets the resting membrane potential.
Some Ca2+ goes back into the stores by SERCA, an active process requiring ATP.
Some Ca2+ is pumped out of the cell by the sodium calcium exchanger.
3:1 Na+:Ca2+ exchange in the sarcolemmal membrane
