Contractile mechanisms Flashcards
What are the three types of muscles?
Skeletal
Cardiac
Smooth
What is contraction?
Contraction is the interaction of actin and myosin fueled by ATP and driven by rise in [Ca2+]
Skeletal vs Cardiac vs Smooth
Striation
Smooth not striated whereas skeletal and cardiac are
Skeletal vs Cardiac vs Smooth
Skeletal have many nucleus
Cardiac usually have one nucleus
What do both skeletal and cardiac muscles have?
Have T-tubules
What are T-tubules?
T-tubules are cell membranes that extend deep into cell interior
What do T-tubules interact with?
Interact with sarcoplasmic reticulum
How are skeletal muscles organised?
Thick filaments made up of myosin
Thin filaments made up of actin
Where two filaments overlap, seen as dark region
What is depolarization initiated by?
Depolarisation initiated by nAchr
What is depolarization maintained by?
Maintained by Na+ channels
What is there within the T-tubules?
Within t-tubules, there are voltage sensing ion channels like proteins which physically interact with Ca2+ in sarcoplasmic reticulum
What is the calcium release channel called?
Ryanodine receptor
What do ryanodine receptors interact with?
Ryanodine receptors interact with DHP
What are DR channel proteins?
Ion channel that doesn’t conduct ions
Why are DR channels known as this?
So called because it is blocked by DHP that are well known calcium channel blockers
Brief overview of contractile mechanism
Tropomyosin lying on actin covering myosin binding site
Calcium binds to troponin and conformational change occurs and myosin binding site on actin is exposed
Contractile cycle(Priming of myosin head)
ATP hydrolysed by ATPase present on myosin head
Cocking of myosin head
Contractile cycle(Power stroke with actin)
Power stroke occurs and ADP is released
Myosin undergoes conformational change
Actin moves towards centre of sarcomere
Contractile cycle(Relaxation of acto-myosin complex
ATP binds to myosin head causing cross bridge to break and myosin head detaches from actin
How does contraction occur in cardiac muscles?
Ion channels in T-tubules pump out Ca2+ into cell
Increased [Ca2+] results in calcium induced calcium release from RyR2
Lead to contraction
Skeletal vs Cardiac
Skeletal:Physical interaction between DHP and RyR
Cardiac:Opening calcium channel promotes CICR
What are smooth muscles not in?
Contractile proteins not in regular arrays:
Not striated
What do smooth muscles not have?
Don’t have a T-tubule system
Smooth muscles have a less developed…
Less developed SR
What are smooth muscles able to sustain?
Sustain contraction for longer periods
What do myofilaments in smooth muscle connect with?
Myofilaments connect with dense bodies
What is present instead of troponin?
No troponin but caldemson and calponin
What does tropomyosin not interact with?
Tropomyosin doesn’t interact with myosin binding site
Difference between the myosin in smooth and skeletal muscles
Myosin in smooth muscles is a different isoform than skeletal muscles
What does myosin have a lower of?
Lower ATPase activity
Lower affinity for ATP
Contraction of smooth muscle
Increased calcium
Calcium binds to calmadulin
Activates myosin light chain kinase which phosphorylates myosin at light chain
What does activation of myosin light chain kinase do?
Phosphorylates regulatory MLC at Ser 19
Increases ATPase activity of myosin lead by 1000x
Alters structure of myosin
Relaxation of smooth muscle and comment on the dephosphorylatoin of myosin
[Ca2+] drops
MLCK becomes inactive
MLCP removes phosphate from Ser 19
But dephosphorylated myosin has a low ATP affinity
Latch state and slow release of actin from myosin
Smooth muscle vs skeletal muscle
Greater shortening in smooth Slower speed of contraction in smooth Lower energy requirement in smooth Greater force generation in smooth Latch state due to myosin having low ATP affinity