Excitation Contraction Coupling in Cardiac and Skeletal Muscle Flashcards by Kaitlyn Stennett

What is a triad?

A triad is the structure formed by a T tubule with a sarcoplasmic reticulum (SR) known as the terminal cisterna on either side

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What is the latency/lag period in skeletal muscle cells?

The time taken from the peak of the action potential/action potential being created and the very onset of contraction of muscle

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What causes the latency/lag period skeletal muscle cells?

The time it takes for the action potential to be transported into the t-tubules to the sarcoplasmic reticulum

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What is significant about the time difference between the action potential and contraction occurring?

Action potential is delivered before contraction occurs

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What happens during an action potential to the skeletal muscle?

1) . ACh is released at the neuro-muscular junction
2) . This activates the ion channels that are on the motor end plate
3) . This causes a net influx of sodium which propagates a muscle action potential as you get a fast depolarisation
4) . The depolarisation travels deep into the t-tubules
5) . The dihydropyridine (DHP) receptors on the Sarcoplasmic reticulum sense voltage and change the conformational change of the channel
6) . This allows DHP to interact with the Ryanodine receptor and open the ryanodine receptor via mechanical coupling, releasing calcium from its stores to the terminal cisterne
7) . Calcium binds to contractile machinery and this causes contraction of the muscle.

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What occurs event occurs in the middle of the latent period between action potential and contraction?

The release of calcium ions

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What happens to calcium after it has caused a contraction?

Calcium is recycled between the sarcoplasmic reticulum/terminal cisternae and the cytoplasm

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How can calcium create an even bigger response?

By activating other Ryanodine receptors and creating a more amplified response

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What are the 2 main differences between skeletal and cardiac muscle calcium?

In skeletal muscle there is no requirement for extracellular calcium during the activation of contraction

In skeletal each t-tubule is sandwiched between 2 terminal cisternae

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What are junctional foot proteins?

The proteins responsible for the calcium response

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What are the 2 junctional foot proteins in skeletal muscle contraction?

Dihydropyridine receptor protein (DHPR) and Ryanodine receptor protein (RYR)

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What is the role of Dihydropyridine receptor protein (DHPR)?

Voltage gated calcium channel in the t-tubule membrane

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What is the role of Ryanodine receptor protein (RYR)?

Calcium release in the Sarcoplasmic reticulum

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What kind of transport is used to take calcium from its store in the sarcoplasmic reticulum down into the muscle cells?

Opening the ryanodine receptors allows a high concentration of calcium ions to flow down into a low concentration of calcium ions in muscle cells - Diffusion

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What does the key event of calcium release cause?

An increase in intracellular calcium concentration which leads to force generation through the interaction of actin and myosin filaments

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What kind of drugs can block the dihyropyridine receptors and prevent calcium being released?

Dihydropyridines

E.g - Nifedipine

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Why are dihydropyridines given?

dihydropyridines are used to treat smooth muscle;

Hypertension
Migrane
Atherosclerosis (plaque builds up inside your arteries)

What drugs can bind to Ryanodine receptors and how does this alter the function of the Ryanodine receptors?

Spasmolytic drugs - act as skeletal muscle relaxant

E.g - Dantrolene

What condition does Dantrolene treat?

Malignant hyperthermia (as this is cause by a mutation of the ryanodine receptors)

What are the main symptoms of malignant hyperthermia ?

Rapid breathing (Tachypnea)
Muscle rigidity
High fever
Increased acid levels in blood and other tissues
Rapid heart rate
Hyperthermia (as quick as rising 1 degree every 5 mins)

What is malignant hyperthermia?

A pharmacogenetic disorder of skeletal muscle;

- Commonly found by people having a severe reaction to commonly used anaesthetics on the operating table

What events happen to relax the skeletal muscle after contraction?

The calcium has to be taken back up into the stores by SERCA (Sarcoplasmic endoplasmic reticulum calcium ATPase) - ATP required as going against concentration gradient

How does SERCA work?

SERCA is triggered by an increase in intracellular calcium concentration in the sarcoplasmic membrane

SERCA actively transports 2 calcium ions from the cytoplasm into the Sarcoplasmic reticulum

What happens after SERCA works?

Muscle relaxes

What does Calsequestrin do?

Calsequestrin stores calcium at high concentrations in the terminal cisternae to establish a concentration gradient from the SR to the cytoplasm

What kind of cells does Cardiac muscle have which makes them different from skeletal muscles and what is the role of this?

Pacemaker cells; - Specialised muscle cells - Unstable resting potential - Undergo automatic rhythmical depolarisation - Have an intrinsic pacemaker ability in SAN

What is special about the depolarisation of pacemaker cells?

They will always depolarise to threshold

What does SAN and AVN stand for and where are they found?

Sino-atrial node - Found in top corner of right atrium Atrio-ventricular node - Found in base of right atrium and top of right ventricle near middle wall of heart

What Neurotransmitters give sympathetic and parasympathetic innervation of cardiac muscle, what action does this cause and where does the innervation occur?

Sympathetic; - Nor-adrenaline - Increases rate and strength - Diffuses Parasympathetic; - Acetyl Choline - Slows rate - Localised to pacemakers

What can intracellular calcium be increase to and what event does this lead to?

Increasing intracellular calcium concentration from < 10^-7 M to > 10^-5 M is the key event which ultimately leads to force generation through interaction of actin and myosin filaments

How would a graph showing cardiac membrane potential charge vary from a skeletal one?

Cardiac muscle graph has no Latent period whereas Skeletal does. After Cardiac muscle reaches its threshold potential is repolarises much slower than Skeletal muscles fast repolarisation

How does 25% of the Calcium required to trigger an action potential enter into the intracellular membrane and what does this trigger afterwards?

Through the L-type Calcium channels (the DHP receptor protein) in the transverse tubular membrane - This isn't enough to trigger a response though! Afterwards this triggers the release of Calcium via the Calcium sensitive (Ryanodine) channels in the Sacroplamic reticulum

What is the absolute requirement for extracellular Calcium in Cardiac muscle?

- 25% through DHPR L-type calcium channel to induce a Calcium induced Calcium release - 75% through the Calcium sensitive/calcium releasing RYR protein in the Sarcoplasmic reticulum

What is a key player in the regulation of Arrythmias?

NCX sodium calcium exchanger

What is the difference between Cardiac muscle in contraction compared to relaxation?

Contraction - DHP receptor and RYR remains open. Calcium is being released from the Sarcoplasmic reticulum stores and is creating a signal to contract the muscle Relaxation - The DHP and RYR are closed. Calcium leaves the muscle to return to the Sarcoplasmic reticulum stores and extrude from the cell via the calcium sodium pump. The muscle relaxes

What 4 steps are required for relaxation in Cardiac muscle?

Requires a decrease in cytoplasmic Calcium concentration from > 10^-5 M to < 10^-7 M Calcium ATPase in Sarcoplasmic reticulum is activated Calcium ATPase in cell membrane pumps out the trigger Calcium Sodium and Calcium exchange in the normal sarcolemmal membrane (3:1 ratio)

How can you differentiate between Skeletal and Cardiac muscles terminal cistern?

Skeletal muscle is a triad Cardiac muscle is a diad because for each terminal cistern it is thought that they only talk with one tubule

What happens to those with malignant hyperthermia who aren't treated?

They will develop respiratory and lactic acidosis, muscle rigidity, and a breakdown of muscle tissue which leads to the release of K+ and thus Hyperkalemia.

What chemically happens in malignant hyperthermia?

The administration of Halothane (anaesthetic) causes excessive ATP hydrolysis to provide energy for contraction This leads to an increased metabolic rate as muscles try to replenish and sustain its ATP stores. Hyperthermia develops because the heat that comes off during the hydrolysis of ATP Malignant hyperthermia is thought to be caused by an abnormality in the release of calcium from the sarcoplasmic reticulum by the Ryanodine receptor (caused by RYR1 gene).

How does Dantrolene work in the post synaptic cell?

Dantrolene blocks excitation contraction coupling between the T tubules and Sarcoplasmic reticulum, stopping the uncontrolled progression of muscle contractions