Physiology Muscles Flashcards
Components of a myosin protein complex
Actin, troponin and tropomyosin
Describe the cross bridge cycle in skeletal muscle
1) ATP binds to myosin head
2) ATP is hydrolysed, myosin head returns to resting position
3) crossbridge forms at new position on actin
4) P is released and conformational change results in power stroke
5) ADP is released
How does Ca2+ regulate contraction?
In a low calcium environment, myosin binding sites are hidden -> High calcium environment, calcium binds to troponin, causing shape change, exposing myosin binding sites so cross bridge cycling can occur
How is Ca2+ released into muscle cell cytoplasm?
- Dihydropyridine receptors (DHPR) volate gated, sense changes in T-tubule membrane potential
- Mechanically coupled to Ryanodine receptors (RYR)
which release calcium from SR to cytoplasm - Influx of calcium initiates cross-bridge cycling + contraction
- Ca2+ is pumped back into SR by SERCA (sarcoplasmic and endoplasmic reticulum calcium ATPase) and this terminates crossbridge cycling
3 factors that influence force of muscle contraction
1) Frequency of Action potentials
2) Number of motor units activated (single motor neuron + innervated muscle fibre)
3) Active length of muscle (muscles have an optimal length for generating maximal force)
Describe how action potentials conducted across the heart
- Sinoatrial node is primary pacemaker region
- action potentials spread from here across atria
- Atrioventricular node is secondary pacemaker, slower rate than SAN
- Conduction propagates slowly through AVN, spreads through ventricular conduction system of purkinje fibres
What is happening to Na+
- ARP (Absolute refractoy period)
- RRP (Relative refractory period)
ARP - nearly all Na+ channels are in the inactivated state
RRP - Na+ channels are recovering from inactivation, the excitability returns towards normal as the number of channels in the inactivated state decreases
Length of the cardiac refractory period?
Long refractory period (200ms)
- Longer ARP compared to RRP
Frank-Starling’s law of the heart?
“the amount of stretch of the cardiac muscle determines the amount of force generated during the 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 of regulating contractile force
Force-length relationship of cardiac muscle - how does it differ? Why is it important?
Cardiac muscle in not able to over-extend unlike skeletal muscle due to strong passive component of tension.
Important because otherwise stretching of cardiac muscle with high venous returns would lead to decreases in force -> failure of cardiac output.
mechanism of increasing force of contraction in the heart?
Adrenaline and nor-adrenaline interaction with ventricular B1-adrenoceptors
- > G Protein coupled receptor
- > activated AC
- > increased production of cAMP
- > cAMP activates P-KA
- > P-KA activates L-calcium channels via phosphorylation -> Influx of calcium -> Contraction
Drugs that increase force of contraction (positive inotropic)
β-adrenoceptor agonists - Isoprenaline, dobutamine
Increase calcium influx through increased cAMP activation
Cardiac glycosides - Digoxin, ouabain
Inhibit Na/K ATPase leading to elevated intracellular Na and reduced calcium efflux by the Na/Ca exchanger
Drugs that decrease force of contraction (negative inotropic)
Calcium channel blockers - verapamil, diltiazem and nifedipine
β-adrenoceptor antagonists – Propanolol, metoprolol
Smooth muscle contraction is regulated by?
- Synaptic inputs from autonomic nervous system
- Circulating hormones, local hormones and metabolites
- The intrinsic activity of pacemaker cells – gap junctions spread depolarisation to neighbouring cells
SR pathways and sarcolemmal pathways smooth muscle for Ca2+ release
SR
- I P3 receptors
- Ryanodine receptors
Sarcolemma
- Voltage gated calcium channels (DHPR/L-type).
- Ligand gated channels (e.g. P2X receptors activated by - ATP & ADP).
- Store operated Ca2+ channels (for refilling SR).
