0429 - Excitation-Contraction Coupling - RM Flashcards
• Describe the sequence of events involved in skeletal muscle contraction starting from synaptic transmission at the neuromuscular junction to the shortening of the sarcomere. • Outline the key proteins involved in contraction and their role in the cross-bridge cycle • Recognise the role of Ca2+ in muscle contraction • Outline the different skeletal muscle types • Describe the mechanisms by which Ca2+ enters and exits skeletal and cardiac muscle cells, and explain how smooth muscle
<p>Describe the sequence of events involved in skeletal muscle contraction starting from synaptic transmission at the neuromuscular junction to the shortening of the sarcomere.</p>
<p>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.</p>
<p>What is a sarcomere?</p>
<p>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.</p>
<p>What protein is responsible for uptake of Ca2+ into the sarcoplasmic reticulum?</p>
<p>SERCA - Sarco/endoplasmic reticulum calcium ATPase.</p>
<p>Sarcomeres contain A bands, H Bands, and I bands. Which of these get shortened during a muscle contraction?</p>
<p>H and I bands – the myosin is effectively inside a cylinder of actin, which it pulls towards the centre M band.</p>
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<p>What are the key proteins involved in muscle contraction?</p>
<p>Most important
Actin
Myosin
Tropomyosin
Tropinin (Complex of T, C, I)
(Less important
Titin
Nebulin)</p>
<p>What is the role of Actin in the cross-bridge cycle?</p>
<p>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.</p>
<p>What is the role of Myosin in the cross-bridge cycle?</p>
<p>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.</p>
<p>What is the role of Titin in muscle contraction?</p>
<p>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.</p>
<p>What is the role of Tropomyosin in the cross-bridge cycle?</p>
<p>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).</p>
<p>What is the Tropinin complex and what is its role in the cross-bridge cycle?</p>
<p>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.</p>
<p>What is the role of Ca2+ in muscle contraction?</p>
<p>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. </p>
<p>What are the two types of skeletal muscle and what is the difference between them?</p>
<p>Fast twitch – fast cross-bridge cycling, glycolytic energy supply, SERCA 1
Slow twitch – slow cross-bridge cycling, oxidative phosphorylation energy supply, SERCA 2.</p>
<p>How does Ca2+ enter and exit skeletal muscle?</p>
<p>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.
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<p>How does Ca2+ enter and exit Cardiac muscle?</p>
<p>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.
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<p>How does Ca2+ enter and exit smooth muscle? How does this differ from striated muscle?</p>
<p>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.</p>
