Block 7 - Muscle physiology Flashcards
How are muscles attached to the bone?
Muscles are anchored to the skelton by tendons.
Muscle cells are very large and aligned in parallel or at a slight angle to the long axis of muscle.
Explain the structure of skeletal muscle
Arranged in a striated pattern, called sarcomeres
A-band that includes the M-band in the centre surrounded by myosin (thick filaments)
Actin partially between myosin layers (thin filaments)
Z lines marking the edges of the sarcomere
What are myofilaments?
Protein complexes that form thick or thin filaments
Thick - formed from large numbers of myosin II molecules
Thin - formed from actin in a complex with troponin and tropomyosin
What are the 5 steps of the cross-bridge cycle?
Cross-bridges between myosin and actin generate force.
1) ATP binds to myosin head
2) ATP is hydrolysed. Myosin head returns to resting position
3) Cross-bridge forms at new position on actin
4) Phosphate is released and conformational changes results in power-stroke
5) ADP is released
How is a signal passed from a nerve to a muscle?
Through the NMJs (neuromusular junctions), the chemical synapses between a nerve and a skeletal muscle fibre.
How does contraction rely on calcium?
Low calcium - resting state - tropomyosin covers the myosin binding sites
High calcium - myosin binding sites are exposed allowing cross-bridge cycling to occur
How is intracellular calcium regulated in skeletal muscle?
Through transverse tubules (T-tubule system) on the sarcolemma and sarcoplasmic reticulum.
Ryanodine receptors on the SR are coupled to dihydropyridine receptors on T-tubules.
Works through excitation-contaction coupling.
What do RYR (ryanodine receptors) do?
Release calcium from SR into the cytoplasm
What are DHPR (dihydropyridine receptors)?
Voltage-gated channels that sense changes in membrane potential in the T-tubles during action potentials
How does excitation-contraction coupling work in skeletal muscle?
1) End plate potentail triggers action potential (AP) in muscle fibre
2) AP propagates along sarcolemma and down transverse tubules (T-tubules)
3) Depolarisation of T-tubules is sensed by dihydropyridine receptors (DHPRs) that are mechanically coupled to ryanodine receptors (RYR) on the sarcoplasmic reticulum (SR).
Voltage dependent calcium release
4) Ca2+ is released into the cytoplasm which initates cross-bridge cycling and muscle contraction.
5) Ca2+ is pumped back into SR by sarcoplasmic and endoplasmuc reticulum calcium ATPase (SERCA) and this terminates cross-bridge cycling.
What are two factors that determine the force of contraction?
1) Frequency of action potentials
2) The number and size of motor units activated
What is a syncitium?
What is the conduction system of the heart?
1) Sinoatrial node (SAN) is the primary pacemaker region
2) Action potentials spread across atria
3) Atrioventriular node (AVN) is the secondary pacemaker region. It also delays conduction to the ventricles
4) Conduction propagates slowly through the AVN and then along the ventricular conducation system consisting of Purkinje fibres
Cardiac refractory periods - explain ARP and RPR
ARP (absolute refractory period) - nearly all Na+ channels are in the inactivated state
RPR (relative refractory period) - Na+ channels are recovering from inactivation, the excitability returns towards the normal as the number of channels in the inactivated state decreases
Why are long cardiac refractory periods physiologically important?
1) Provides time for calcium transient and contractile force to decrease before the start of the next cardiac cycle.
- Cardiac muscle relaxation has to occur for refillingof ventricles
2) Protects the heart against arrhythmias
Where are action potentials generated in the cardiac muscle?
Generated sponataneously in pacemaker cells in the SAN and spread across the heart because cells are electrially coupled by gap-junctions
Why is the cardiac msucle a syncitium?
Because all cells are electrically coupled to one another via gap junctions
How does calcium release work in cardiac muscle?
Ca2+ release from the SR occurs by calcium induced calcium release.
1) Action potential is conducted down T-tubules
2) Depolarisation opens voltage gates Ca2+ channels (similar to SK DHPRs) - causing calcium influx
3) RYRs open because of the rise in Ca2+ concentration (RYRs functioning as ligand-gated Ca2+ channels)
4) Ca2+ from SR enters cytoplasm thorugh RYRs (= Ca2+ induced Ca2+ release) which leads to contraction
5) Ca2+ rise is transient as Ca2+ is pumped back into SR by SERCA or removed by a Na+/Ca2+ exchanger
What is Frank-Starling’s law of the heart?
“the mechanical energy set free in the passage from the resting to the active state is a function of the length of the fibre”
ie. the amount of stretch of the cardiac muscle determines the amount of force generated during contraction.
The amount of blood returning to the heart determines how much the cardiac muscle is stretched and thus how much force is generated (intrinsic mechanism for regulating contractile force).
Why can cardiac muscle not overextend like skeletal muscle can?
Because there is a strong passive component of tension.
Important as otherwise the stretching of the cardiac muscle with high venous returns would lead to decreases in force and failure of cardiac output.
Explain how inotropy in the heart works
Both blood-bourne adrenaline and sympathetically released noradrenaline can interact with beta1-adrenoceptors to increase the force of contraction (+ve inotropy).
Cause an increase in calcium and contractility.
List two positive inotropic drugs and their uses
1) Beta-adrenoceptor agonists - adrenaline, noradrenaline, dobutamine
- Raise cAMP and activate protein kinase A
- Increase calcium currents and calcium release from SR
- Adrenaline is used to treat shock and cardiac arrest
- Dobutamine is sometimes used for acute heart failure
2) Cardiac glycosides - digoxin and ouabain
- Inhibit Na/K ATPase leading to elevated intracellular Na and intracellular calcium
- Digoxin is used to treat heart failure
List two negative inotropic agents and their uses
1) Calcium channel blockers - verapamil, diltiazem and nifedipine.
- Used to treat cardiac arrhythmias and angina
2) beta-adrenoceptor antagonists - propanolol, bisoprolol, metoprolol.
- Used clinically for treating angina, hypertension and cardiac arrhythmias
Where is smooth muscle found?
In the walls of blood vessels and many ‘hollow’ or tubular organs such as the stomach and intestines
