Excitation Contraction Coupling in Cardiac and Skeletal Muscle

Question 1

What is excitation contraction coupling?

Answer 1

• 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)

Question 2

describe action potential

Answer 2

Action potential is the minimum voltage required to cause a rapid depolarisation of the membrane potential followed by a rapid repolarisation

Question 3

What is the latent period in regards to action potential?

Answer 3

The time it takes to repolarise the membrane potential after depolarisation due to action potential being reached

Question 4

What is the role of the transverse tubule?

Answer 4

• 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

Question 5

What two intracellular compartments is calcium recycled between?

Answer 5

– Sarcoplasmic reticulum/terminal cisternae

– Cytoplasm

Question 6

How much Ca2+ is required during the activation of contraction?

Answer 6

None

Question 7

What type of proteins are essential to the mechanism of Ca2+ release?

Answer 7

Junctional foot proteins

Question 8

What two junctional foot proteins are essential for Ca2+ release?

Answer 8

– 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)

Question 9

What occurs when calcium channels release?

Answer 9

• 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

Question 10

What is the key event which ultimately leads to force generation through the interaction of actin and myosin filaments?

Answer 10

The increase in intracellular calcium concentration

Question 11

What are dihydropyridines?

Answer 11

• Voltage-gated Ca2+ channel blocking drugs

– Nifedipine

Question 12

What are dihydropyridines used to treat?

Answer 12

Used to treat (smooth muscle)
– Hypertension
– Migraine
– Atherosclerosis

Question 13

What type of drug is ryanodine?

Answer 13

• Spasmolytic drug acting as a skeletal muscle relaxant

– Dantrolene

Question 14

What is Ryanodine used to treat?

Answer 14

Used to treat (sarcoplasmic reticulum)
– Muscle spasm
—-• Malignant hyperthermia

Question 15

What are ryanodine receptor type 1 channel mutations associated with?

Answer 15

Malignant hyperthermia

Question 16

What is malignant hyperthermia?

Answer 16

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

Question 17

What are the symptoms of malignant hyperthermia?

Answer 17

• Muscle rigidity
• High Fever
• Increased acid levels in blood and other tissues
• Rapid heart rate

Question 18

What is the underlying mechanism of malignant hyperthermia?

Answer 18

Point mutations in the gene coding for RyR1

Ryanodine receptor type 1

Question 19

What opens RYR channel electro-mechanical coupling?

Answer 19

Protein-protein interaction

Question 20

What is SERCA?

Answer 20

Sarcoplasmic Endoplasmic Reticulum Calcium ATPase, otherwise known as Ca2+ ATPase

Question 21

What is the role of SERCA?

Answer 21

• 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

Question 22

What is the role of calsequestrin?

Answer 22

• 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

Question 23

What are pacemaker cells?

Answer 23

• Specialised muscle cells - found in cardiac muscle
• Unstable resting potential
• Undergo automatic rhythmical depolarisation

Question 24

Where are pacemaker regions found?

Answer 24

In the sino-atrial node and the atrio-ventricular node

Question 25

What neurotransmitter is responsible for inducing a parasympathetic effect on cardiac muscle and what action does this effect take?

Answer 25

Acetyl Choline

Slows rate

Question 26

Where is the innervation of the parasympathetic system on cardiac tissue?

Answer 26

Localised to pacemakers

Question 27

What neurotransmitter is responsible for inducing a sympathetic effect on cardiac muscle and what action does this effect take?

Answer 27

Nor-adrenaline

Increases rate and strength of contractions

Question 28

Where is the innervation of the sympathetic system on cardiac tissue?

Answer 28

diffuse across the cardiac myocytes

Question 29

Discuss Ca2+-induced Ca2+ release (CICR) in cardiac muscle

Answer 29

• 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

Question 30

Discuss Ca2+ in cardiac muscle

Answer 30

• 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

Question 31

Discuss relaxation in cardiac muscle

Answer 31

• 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)

Question 32

What are spasmolytic drugs?

Answer 32

drugs that are able to relieve spasm of smooth muscle