0429 - Excitation-contraction coupling - RM

Question 1

Describe the sequence of events involved in skeletal muscle contraction starting from synaptic transmission at the neuromuscular junction to the shortening of the sarcomere.

Answer 1

1. ACh from an α-motor neuron crosses the synaptic cleft at the neuromuscular junction, opening Na+/K+ Channels.2. AP propagates along sarcolemma and through T-Tubules, which are surrounded by sarcoplasmic reticulum (the Triad).3. Depolarisation of the triad opens V-gated Ca2+ channels, releasing Ca2+ into the T-Tubule.4. Ca2+ binds to Actin filaments, causing a conformational change that allows the Myosin head (with partially-hydrolised ATP) to bond to the Actin, forming a CROSS BRIDGE.5. Myosin head releases ATP, undergoing a conformational change, pulling actin to centre of sarcomere, shortening sarcomere.

Question 2

What is a sarcomere?

Answer 2

The basic unit of muscle contraction - A length of myofibril demarcated by two Z lines, with an M band in the middle. Myosin bonds to the M band, while Actin and Titin bond to the Z-lines. The bands of sarcomeres give skeletal and cardiac muscle their striated appearance.

Question 3

What protein is responsible for uptake of Ca2+ into the sarcoplasmic reticulum?

Answer 3

SERCA - Sarco/endoplasmic reticulum calcium ATPase.

Question 4

Sarcomeres contain A bands, H Bands, and I bands. Which of these get shortened during a muscle contraction?

Answer 4

H and I bands – the myosin is effectively inside a cylinder of actin, which it pulls towards the centre M band.

Question 5

What are the key proteins involved in muscle contraction?

Answer 5

Most importantActinMyosinTropomyosinTropinin (Complex of T, C, I)(Less importantTitinNebulin)

Question 6

What is the role of Actin in the cross-bridge cycle?

Answer 6

It is the thin filament, and is moved by fixed myosin – Myosin attaches to Actin, forming a cross bridge, and moves the actin via a conformational change, contracting the sarcomere.

Question 7

What is the role of Myosin in the cross-bridge cycle?

Answer 7

The thick filament that moves actin – Myosin attaches to Actin, forming a cross-bridge, and moving the actin via a conformational change, thus contracting the sarcomere.

Question 8

What is the role of Titin in muscle contraction?

Answer 8

Provides elasticity in the sarcomere by acting as a spring connecting the Z-disk to the M line. No role in the actual mechanisms of the cross-bridge cycle.

Question 9

What is the role of Tropomyosin in the cross-bridge cycle?

Answer 9

Coils around actin like a rope, and covers the myosin binding sites on the actin until moved by a conformational change when it binds to Tropinin T. As it moves, it facilitates the exposure of adjacent myosin binding sites (like uncoiling a strand of rope).

Question 10

What is the Tropinin complex and what is its role in the cross-bridge cycle?

Answer 10

Consists of Tropinins T, C, and I. TnT bonds to tropomyosin (and thus actin), while TnC binds to Ca2+ when it is present. The presence of calcium on TnC forces a conformational change on the complex, which also moves the tropomyosin and exposes the myosin-binding site on the actin, allowing the myosin-actin cross-bridge to form.

Question 11

What is the role of Ca2+ in muscle contraction?

Answer 11

Ca2+ is the key ion for muscle contraction – Ca2+ release from the SR commences the cross-bridge cycle, by forcing a conformational change that allows myosin to bond to actin.

Question 12

What are the two types of skeletal muscle and what is the difference between them?

Answer 12

Fast twitch – fast cross-bridge cycling, glycolytic energy supply, SERCA 1Slow twitch – slow cross-bridge cycling, oxidative phosphorylation energy supply, SERCA 2.

Question 13

How does Ca2+ enter and exit skeletal muscle?

Answer 13

Extracellular Ca2+ is not essential. Ca2+ is released into T-tubules from the SR via V-gated Ca2+ channels when an AP is propagated. From here it is a key element of the cross-bridge cycle until it is reuptaken by a SERCA pump.Ca2+ can also enter via v-gated L-type Ca2+ channels, triggering SR release of Ca2+ via electromechanical coupling.

Question 14

How does Ca2+ enter and exit Cardiac muscle?

Answer 14

Extracellular Ca2+ is essential. Ca2+ enters the cell via V-gated L-type Ca2+ channels. This initiates the release of Ca2+ from the SR via electrochemical coupling, allowing the cross-bridge cycle to proceed. It is removed via SERCA pump (limited) a 3Na+/1Ca2+ exchanger, or a sarcolemmal Ca2+ pump.Ca2+ levels can regulate the force of contraction.

Question 15

How does Ca2+ enter and exit smooth muscle? How does this differ from striated muscle?

Answer 15

Many more ways than for striated muscle. Ca2+ can enter smooth muscle via V-gated channels (as with skeletal and cardiac). However, APs are not always needed – smooth muscle can open ligand-gated channels to facilitate the movement of Ca2+, and thus contraction, in a second-messenger cascade. This is known as pharmomechanical coupling.

Question 16

What are some differences and similarities between skeletal, cardiac, and smooth muscle?

Answer 16

Cardiac and skeletal = striated, but not smoothSmooth and cardiac = mechanical and electrical synctia, but not skeletalSmooth and cardiac = autonomic NS, skeletal = somatic NSSmooth = phasic and tonic contractions, cardiac = phasic, skeletal = on-demand.Skeletal = multiple nuclei, cardiac and smooth = one per cell.

Question 17

How is skeletal muscle contraction controlled and coordinated?

Answer 17

AP from alpha-motor neuron leads to Ca2+ release from SR and, together with ATP, muscle contraction. Coordinated in primary motor cortex.

Question 18

How is cardiac muscle contraction controlled and coordinated?

Answer 18

AP from sinoatrial node (itself under control of ANS) depolarises the atria, causing atrial contraction. On reaching atrioventricular note, the depolarisation slows down contraction, and AP spreads through purkinje fibres to coordinate contraction of ventricles. Gap junctions in cells also allow coordinated contractions.

Question 19

How is smooth muscle contraction controlled and coordinated?

Answer 19

Contraction is dependant on relative Ca2+ levels. Can be initiated by AP, intrinsic ‘pacemaker’ cells, or hormones. Coordination comes from attachments (primarily gap junctions, also adherens junctions, dense bodies, and caeolae).

Question 20

What are the 5 stages of the cross-bridge cycle?

Answer 20

1 – Resting state. Myosin has partially hydrolysed ATP.2 – Cross Bridge state. Ca2+ bonds to TnC, allowing Myosin to bond to actin, forming cross-bridge.3 – Power-stroke state – Myosin head releases Pi, undergoing a conformational change that pulls on the actin filament.4 – Attached state – Myosin has released ADP, but is still attached (rigor mortis)5 – Released state – ATP binds to myosin, breaking the cross bridge, and returning it to resting state.