Excitation coupling in cardiac and skeletal muscle Flashcards
In the neuromuscular junction, what is the name of the receptors found on the skeletal muscle fibre and what is its role?
Nicotinic receptor
• Acetylcholine receptor
• Primary receptor in the muscle for motor nerve-muscle communication
What is the latent period?
The lag onset of the action potential- the time taken for the muscle to contract from the peak action potential
Describe the stages of depolarisation
- Somatic motor neurone releases Acetylcholine at neuromuscular junction
- Net entry of Na+ through Acetylcholine receptor channel initiates a muscle action potential
What is the role of the transverse tubule?
- the action potential is propagated from the end plate along the surface of the muscle fibre and then does into the fibre down the T tubule membrane
- The depolarisation of the T tubule membrane is signalled to the membrane of the terminal cisternae (SR)
What 2 compartments are calcium recycled between?(intracellularly)
- Sarcoplasmic reticulum/ terminal cisternae
* Cytoplasm
What are the two junctional foot proteins?
- Dihydropyridine receptor protein (DHPR)
* Ryanoidine receptor protein (RYR)
Describe the Dihydropyridine receptor protein
- L type voltage gated calcium channel
* Located in the T tubule membrane
Describe the Ryanodine receptor protein
• Calcium release channel in the sarcoplasmic reticulum
main calcium channel in th SR
Describe the stages of mechanical coupling in the muscle fibre and how this causes contraction
- Membrane depolarisation opens the L type Ca2+ channel (DHPR)
- Mechanical coupling between the DHPR and RYR channel cause the RYR channel to open
- Ca2+ exits the sarcoplasmic reticulum and activates troponin C, leading to muscle contraction
(4. Ca2+ entering the cell via the DHPR channels can also activate the RYR release channels but this is not essential in skeletal muscle contraction)
Describe what happens after the action potential in a t tubule has caused the conformation of the DHP receptor to be altered (up to cross bridges forming)
- The DHP receptor opens Ca2+ release channels (RYR) in the sarcoplasmic reticulum and Ca2+ enters the cytoplasm
- Ca2+ binds to troponin allowing strong actin-myosin binding
What is Dantrolene and what is it used to treat?
A spasmolytic drug thought to work on the ryanodine receptor that acts as a skeletal muscle relaxant (it may reduce the calcium release)
• Used to treat: (sarcoplasmic reticulum)
• Malignant hyperthermia
What is Nifedipine and what is it used to treat?
- A Dihydropyridine blocker- blocks voltage gated Ca2+ channels
- Used to treat: (smooth muscle)
- Hypertension
- Migrane
- Atherosclerosis
What is malignant hypothermia?
Pharmocogenetic disorder of skeletal muscle
• It is the result of a severe reaction to commonly used anaesthetics and depolarising muscle relaxants
• First manifestations of malignant hypothermia occur in the operating room
• It is fatal if left untreated
What are the symptoms of malignant hypothermia?
- Muscle rigidity
- High fever
- Increased acid levels in blood and other tissues
- Rapid heart rate
What is the underlying mechanism of Malignant hypothermia?
A point mutation in the gene coding for RyR1
What is and what is the role of SERCA?
- Sarcoplasmic Endoplasmic reticulum calcium ATPase
- Works against the gradient to force calcium back into the stores (into the SR) by hydrolysing ATP (2 Ca2+ ions per molecule ATP) (activated by the increase in intracellular calcium concentration)
- Therefore decreases the concentration of calcium ions in the cytoplasm
At around what level of Ca2+ does the muscle relax?
Less than 10-7 M
What is the role of calsequestrin
• Stores calcium at high concentrations in the terminal cisternae to establish a concentration gradient from the SR to the cytoplasm
What is calsequestrin?
- A calcium binding protein
* Molecular Weight 44000
How many calcium ions can bind per molecule of calsequestrin?
43
Aside from appearance (striations, nuclei) how do cardiac muscle cells differ from skeletal muscle cells?
- Unstable resting potential
* Undergo automatic rhythmical depolarisation
What is the Parasympathetic neurotransmitter of cardiac muscle, what is its action and innervation?
- Acetylcholine
- Slows the rate of contraction
- Localised to pacemakers
What is the Sympathetic neurotransmitter of cardiac muscle, what is its action and innervation?
- Noradrenaline
- Increases rate and strength of contractions
- Diffuse
What calcium concentration ultimately leads to the force generation in cardiac muscle?
10-5 M
What is the resting potential of cardiac muscle?
-90mV
How does the shape of a cardiac muscle action potential graph differ to that of skeletal muscle
In a cardiac muscle action potential graph, there is:
• A more rapid depolarisation
• A plateau period
• Then a repolarisation
What is the resting potential of skeletal muscle?
-70mV
What is the threshold potential of skeletal muscle?
-55mV
What is the ratio of Na+ to Ca2+ of exchange in the sarcolemmal membrane?
3:1
What is excitation contraction coupling?
Describes the series of events between the excitation of the muscle fibre membrane and the onset of contraction
Why do we get a latent period?
To bring the impulse deep into the muscle fibre
What is the t tubule?
An invagination of the plasma membrane
In which regions of the heart are the pacemaker cells?
- The sino-atrial node
* Atrio-ventricular node
What, regarding depolarisation, is special about pacemaker cells?
They always depolarise to the threshold
What percentages of calcium required for muscle contraction come from each receptor?
- 25% from DHPR
* 75% from RYR
