Excitation Contraction Coupling in Cardiac and Skeletal Muscle Flashcards
What is excitation contraction coupling?
• Linkage between excitation of the muscle fibre membrane and the onset of contraction
(Links excitation of the muscle fibre membrane and the onset of contraction)
describe action potential
Action potential is the minimum voltage required to cause a rapid depolarisation of the membrane potential followed by a rapid repolarisation
What is the latent period in regards to action potential?
The time it takes to repolarise the membrane potential after depolarisation due to action potential being reached
What is the role of the transverse tubule?
- Action potential is propagated from the end plate along the surface of the muscle fibre (sarcolemma)
- Action potential is propagated into the fibre down the T-tubule membrane
- Depolarisation of the T-tubule membrane is ‘signalled’ to the membrane of the terminal cisternae
What two intracellular compartments is calcium recycled between?
– Sarcoplasmic reticulum/terminal cisternae
– Cytoplasm
How much Ca2+ is required during the activation of contraction?
None
What type of proteins are essential to the mechanism of Ca2+ release?
Junctional foot proteins
What two junctional foot proteins are essential for Ca2+ release?
– Dihydropyridine receptor protein (DHPR)
—-• L-type voltage-gated calcium channel in the T- tubule membrane
– Ryanodine receptor protein (RYR)
—-• Calcium release channel in the SR
(Think abt the £2.50 Ryan owes you for that fucking wine)
What occurs when calcium channels release?
- The open calcium channels allow calcium to diffuse down a steep concentration gradient into the cytoplasm
- Cytoplasmic calcium concentration increases from < 10-7 M to > 10-5 M
- The increase in intracellular calcium concentration is the KEY event which ultimately leads to force generation through the interaction of actin and myosin filaments
What is the key event which ultimately leads to force generation through the interaction of actin and myosin filaments?
The increase in intracellular calcium concentration
What are dihydropyridines?
• Voltage-gated Ca2+ channel blocking drugs
– Nifedipine
What are dihydropyridines used to treat?
Used to treat (smooth muscle)
– Hypertension
– Migraine
– Atherosclerosis
What type of drug is ryanodine?
• Spasmolytic drug acting as a skeletal muscle relaxant
– Dantrolene
What is Ryanodine used to treat?
Used to treat (sarcoplasmic reticulum)
– Muscle spasm
—-• Malignant hyperthermia
What are ryanodine receptor type 1 channel mutations associated with?
Malignant hyperthermia
What is malignant hyperthermia?
Pharmacogenetic disorder of skeletal muscle
• Severe reaction to commonly used anaesthetics and depolarising muscle relaxants
• First manifestations of MH occur in the operating room
• Fatal if untreated
What are the symptoms of malignant hyperthermia?
- Muscle rigidity
- High Fever
- Increased acid levels in blood and other tissues
- Rapid heart rate
What is the underlying mechanism of malignant hyperthermia?
Point mutations in the gene coding for RyR1
Ryanodine receptor type 1
What opens RYR channel electro-mechanical coupling?
Protein-protein interaction
What is SERCA?
Sarcoplasmic Endoplasmic Reticulum Calcium ATPase, otherwise known as Ca2+ ATPase
What is the role of SERCA?
- The increase in intracellular calcium concentration activates a Ca2+ ATPase (calcium pump) in the SR membrane
- Active transport of calcium from the cytoplasm into the SR (2 Ca2+ ions per molecule ATP hydrolysed)
- [Ca2+] decreases to <10-7M - RELAXATION
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
– Calcium binding protein
– MW 44000
– Binds 43 Ca2+ ions per molecule
What are pacemaker cells?
- Specialised muscle cells - found in cardiac muscle
- Unstable resting potential
- Undergo automatic rhythmical depolarisation
Where are pacemaker regions found?
In the sino-atrial node and the atrio-ventricular node
What neurotransmitter is responsible for inducing a parasympathetic effect on cardiac muscle and what action does this effect take?
Acetyl Choline
Slows rate
Where is the innervation of the parasympathetic system on cardiac tissue?
Localised to pacemakers
What neurotransmitter is responsible for inducing a sympathetic effect on cardiac muscle and what action does this effect take?
Nor-adrenaline
Increases rate and strength of contractions
Where is the innervation of the sympathetic system on cardiac tissue?
diffuse across the cardiac myocytes
Discuss Ca2+-induced Ca2+ release (CICR) in cardiac muscle
- 25% of the required Ca2+ enters though the L-type Ca2+ channels (DHP receptor protein - DHPR) in the transverse tubular membrane
- Triggers the release of Ca2+ via the Ca2+ sensitive (ryanodine) channels in the SR
Discuss Ca2+ in cardiac muscle
• Absolute requirement for extracellular Ca2+
– Approximately:
—-• 25% enters through the DHPR L-type calcium channel to induce CICR
—-• 75% through the calcium sensitive calcium release RYR protein in the SR
Discuss relaxation in cardiac muscle
• Requires a decrease in cytoplasmic Ca2+ concentration from
>10-5 M to < 10-7 M (molar units)
• Ca2+ ATPase in sarcoplasmic reticulum is activated
• Ca2+ ATPase in the cell membrane pumps out the trigger Ca2+
• Na+:Ca2+ exchange in the sarcolemmal membrane (3:1)
What are spasmolytic drugs?
drugs that are able to relieve spasm of smooth muscle
