The signal for muscle contraction Flashcards
What is signal transduction ?
Conversion of information from one form to another, e.g. electrical to chemical during neurotransmission at synapses
Skeletal muscle contraction is regulated by ?
A Ca2+-dependent thin filament-based regulatory mechanism
Sarcomere Ca2+ concentration is regulated by ?
Release and uptake into the sarcoplasmic reticulum (SR)
Motor axons synapse with the muscle fibre at the ?
Neuromuscular junction (NMJ)
Explain signal for contraction ?
- An action potential stimulates voltage-gated Ca2+ channels in the axon to open (1)
- The Ca2+ influx causes fusion of vesicles and release of Ach into the synaptic cleft
- Ach binds to the NiAchR on the muscle cell plasma membrane (2)
- The NiAchR opens, and Na+ ions flow in causing a local depolarisation, activating voltage-gated Na+ channels, leading to an action potential (3)
- The AP activates DHP receptors on the T-tubules (4)
- In turn, DHPRs activate RyRs on the SR, leading to calcium release (5)
How are neurotransmitters synthesised and stored ?
Neurotransmitter synthesised in the cytoplasm and stored in vesicles
How is acetylcholine broken down ?
Broken down (hydrolysed) by acetylcholinesterase
What does acetylcholine bind to?
Acetylcholine binds to nicotinic ACh receptors on the muscle cell
What are the two main classes of acetylcholine receptor ?
- Nicotinic = selectively activated by nicotine (from tobacco)
- Muscarinic = activated by muscarine (from the mushroom Amanita muscaria)
What is the Nicotinic Ach receptor ?
Ionotropic meaning it is directly linked an ion channel (metabotropic receptors use second messengers)
What is a nicotine addiction due to ?
The action of nicotine on nACh receptors in the brain
What can influence the neuromuscular junction ?
Many toxins/venoms, e.g. sarin
What is Myasthenia gravis ?
This is an autoimmune disorder in which antibodies are formed against the nicotinic receptor
What are changes in nAChR expression linked to ?
A wide variety of neurological and psychiatric disorders
What 5 subunits contribute to channel ?
- Two acetylcholine-binding sites (alpha subunits)
- One each of beta, gamma and delta
- Each subunit has four membrane-spanning α helices, M1–M4
What forms the wall of the channel ?
Amphipathic M2 helices - others are hydrophobic to embedded in the membrane
What is caused when acetylcholine binds to nAChr ?
It causes a rapid influx of sodium, depolarising the membrane
What is at the centre of the nAChr receptor ?
There is a ring of bulky hydrophobic leucine residues constricting the channel and keeping it closed
When acetylcholine binds to nAChr what does it induce ?
- Acetylcholine induces rotation in M2 subunits, moving these leucine residues away and replacing them with polar residues, opening channel
- Rapid influx of Na+ ions
What does membrane depolarisation activate ?
It activates voltage-gated sodium channels, causing further influx of sodium, leading too an action potential
Where does depolarisation spread to ?
It spreads down muscle membranes into T-tubules
What does depolarisation activate on the T-tubule membranes ?
Dihydropyridine (DHP) receptors
What does depolarisation activate on the T-tubule membranes ?
Dihydropyridine (DHP) receptors
In turn, what do these DHP receptors activate ?
Ryanodine receptors (RyR) on the sarcoplasmic reticulum causing opening and release of Ca2+ into cytoplasm
What is the largest known ion channel ?
Ryanodine receptor Ca2+ channel
What do DHPRs sense ?
Membrane depolarisation and transmit conformation change to the RyR causing the channel to open and release Ca2+ from the store: excitation-contraction coupling
What happens when calcium ions bind to troponin C ?
- It causes the troponin complex to rotate
- This removes the tropomyosin blockage of the myosin binding sites
- Myosin can now bind the actin filaments and initiate contraction
What does creatine kinase catalyse ?
It catalyses the formation of ATP from phosphocreatine and ADP. As a last resort, myokinase can combine 2ADP to make ATP and AMP
What is used as energy for resting muscles ?
Fats, but these take time to break down
