Muscle Contraction Flashcards
The different structural features of the three muscle types.
Muscles Types:
• Skeletal/Striated
• Cardiac
• Smooth
The different mechanisms by which a rise of calcium is generated in the different muscle cells.
Contraction – shortening of the cell by a molecular interaction between two proteins called actin and myosin, which interact, fuelled with ATP hydrolysis and driven by a rise in intracellular calcium
A) Linkage between membrane events (excitation) and rise in calcium
B) Mechanism that a rise in calcium produces contraction
The different components of the contractile apparatus including the features of actin and myosin.
• Na+ channel blockers in cardiac or skeletal – no contraction, very little happens in smooth
• Myosin/actin present in all muscles
• Ca2+ - sensor: senses rise in calcium
Actin
• Thin filament kept localised against Z-disk by a support molecule called alpha-actinin
• Z-line where Z-disk is
• M-line – has little interaction
Myosin
• Anti-parallel molecules of myosin, with central bare zone where tails are overlapping
• Myosin molecule has a hinge in it
The biochemical mechanisms that link a rise in calcium with interaction of actin and myosin in SKELETAL MUSCLE
- Thin and thick filaments are complexes of protein
- Lie in highly organised structure, and basic unit = sarcomere
- Muscle cells therefore look striated from X-ray bouncing off different densities
• Thick filament – made mainly of myosin
o Myosin contains of tail and head which contains an ATPase
• Thin filament – very complex o Consists of actin, which has a myosin binding site, Tropomyosin which covers the myosin binding site head in absence of calcium Troponin complex • Troponin-C = senses and binds calcium • Troponin –T = binds tropomyosin o Alpha-actinin binds actin to Z-disk
Mechanism 1:
• Myosin-actin interact by calcium binding to troponin, causing interactions which allows tropomyosin inhibition to be removed
• At rest, tropomyosin is preventing by blocking site on actin molecules
• Ca2+ rises, binds to troponin C, causes it to bind to troponin T which binds to tropomyosin to remove it
Skeletal structure
1) Cell membrane made of phospholipid bilayer
2) Intracellular membrane for Sarcoplasmic Reticulum
3) Sodium ion channels
4) T-tubule system – invagination of cell membrane
Brings membrane event deep in cell
5) DHP (dihydropyradine) receptors - as they block calcium channels or sense voltage changes
There is a physical interaction between sarcoplasmic reticulum and DHP receptor
6) Calcium release channels in SR called Ryanodine receptors (RYR2)
7) SR has pump to take Ca2+ back in for cell homeostasis and also has Na+/Ca2+ exchanges
Skeletal mechanism
- Motor nerves release the neurotransmitter Ach, which interacts with nicotinic acetylcholine receptors
- Nicotinic Ach receptors open, allowing influx of Ca2+
- This causes a wave of depolarisation in membrane potential
- Opens sodium channels
- Sodium dependant action potential spreads down t-tubule
- This causes a conformational change to the structure of DHP receptors and has a physical effect on calcium release channels in sarcoplasmic reticulum called Ryanodine receptors
- A lot of Ca2+ is released from the sarcoplasmic reticulum
- Calcium influx is limited but a lot of Ca release from SR
- Rise in calcium interacts with troponin and leads to contraction
Cardiac structure
- T-tubule present
- SR involved
- Ryanodine receptors leaking out calcium
- Calcium interacts with troponin to lead to contraction
- Sodium channels involved
- No nicotinic acetyl choline receptors driving this
- Major difference between cardiac and skeletal - No physical interaction
Cardiac mechanism
- The impulse for contraction of cardiac muscle is in pacemaker region (SAN nucleus starts depolarisation and allows Na+ channels to open)
- This causes a sodium driven depolarisation down the t-tubule
- A functional calcium channel, allows calcium to come in
- The Ryanodine channels open by a local rise in calcium
- Calcium induced calcium release (CICR)– not physical interaction
- A compromise in this mechanism can lead to heart failure
Smooth structure
• No t-tubule
• SR involvement is varied
• Calcium channels bring in a lot of calcium
The receptors for smooth muscle contraction via GPCR
Smooth mechanism
- Alpha-Gq/G11 phospholipase C converts PIP2 into IP3 and DAG
- IP3 interacts with its receptors called IPR and get calcium influx
- Some smooth muscle cells also have Ryanodine receptors
- Ryanodine receptors get Ca2+ influx by calcium induced calcium released
- Ca2+ binds to calmodulin, not troponin
Sliding filament model of muscle contraction
Generalised contractile cycle – 5 myosin head cycles / second
- Rise in calcium has removed tropomyosin by binding to troponin in skeletal and cardiac muscles
- Actin now revealed myosin binding site
- ATP binds to myosin and gets hydrolysed = Myosin-ADP
- This causes myosin to kink, and bend around hinge
- Calcium, myosin –ADP bind to actin and get myosin-ADP-actin complex
- ATP – myosin and actin dissociate and are ready to interact again
- Myosin molecule, ATP binds and hydrolysed – power stroke ready
- Free binding site, ATP introduced, unbind and powered again.
- Unbinding and binding driven by ATP hydrolysis
Rigor mortis
- Rigor mortis (stiff muscles when death) – dying muscle cells releases calcium and sufficient ATP to give contraction. Since there is no more ATP generation the actin and myosin can’t unbind.
Detailed contraction
- Tropomyosin covers actin binding site on actin when at rest
- Contraction begins when Ca2+ ion binds to troponin causing conformational change – allows actin to interact with ‘primed’ myosin
- This exposes active site along F-actin strand
- Myosin head has ADP and Phosphate bound to it and binds to active site
- When binding, the phosphate is released
- This release strengthens myosin-actin bond and initiates power stroke
- This pivots the myosin head and pulls actin to centre of sarcomere
- After pivoting, ADP dissociates
- ATP attaches to empty nucleotide binding site
- This binding causes the myosin head to detach from actin filament
- ATP is hydrolysed, releasing energy which moves myosin head back to pre-stroke state
- Myosin uses energy from ADP and Pi to form more cross bridges with actin and begin another cycle
- Shortens sarcomere and contracts muscle
- When Ca2+ is depleted or reabsorbed, Ca2+ ions detach from troponin
- Troponin and tropomyosin return to position covers actin binding site
- Actin slides back to original position causing relaxation of the muscle
The biochemical mechanisms that link a rise in calcium with interaction of actin and myosin in SMOOTH MUSCLE
- Contractile proteins not arranged in organised manner (no z-disc/ sarcomere structure)
- Myosin has low ATPase activity
- Regulatory light chain
- The actin is longer than skeletal muscles
- No troponin but regulatory proteins called Caldesmon and Calponin
- Myofilaments connect with dense bodies
- Dual regulation (MLCK/MLP)
- Rise in calcium – doesn’t bids to troponin
- Binds to different calcium sensor called Calmodulin
- 4 molecules of calcium bind to calmodulin
- they don’t remove something suppressive, but stimulate myosin light chain kinase (MLCK)
- Activation of myosin light chain kinase phosphorylates regulatory myosin light chain (MLC) at serine 19
- Causes ATPase activity to increase 1000-fold for ATP turnover.
- Structure of myosin changes
- Smooth muscle doesn’t have organised contractile proteins
- Arranged as membrane dense areas – proteins form network across the cell
- As smooth muscle contracts, it doesn’t shorten but more like shrivels
Performance smooth (better) vs skeletal muscle
• Greater shortening in smooth vs skeletal – longer actin
• Slower speed of contraction than skeletal muscle (30x)
o ATPase activity binds and unbinds quicker and so can power stroke quicker
o smooth muscle lazier as it binds with ADP longer.
• Lower energy requirement in smooth muscle than skeletal muscle (latch state)
o Can maintain contraction as actin has low ATP affinity
• Greater force generation in smooth vs skeletal
o Smooth maintains contraction for longer with less energy demand
• Longer contraction, lower energy requirement
- Turn on mechanism: phosphorylation of MLC making the myosin work more
- Turn off – need phosphatase (take off phosphatase group)
- Smooth muscle can maintain contraction with low calcium levels
- Because phosphatase is inhibited by many different things
- In hyper contractile states (asthma or hypertension - where smooth muscles are hypercontracted) myosin phosphatase is inhibited
- Myosin light chain stays phosphorylated
- Rise in calcium causes MLCK to increase activity, myosin in phosphorylated, and there is an increase ATPase activity which maintains contraction
