Nueromuscular Junction and excitability Flashcards
week 2
What is nebulin?
cytoskeleton element that stabilizes thin filaments and anchors it to Z line
What is the role a triad?
AP on surface not effective to stmulate deeper organelles so T-tubules bring depolarization into interior.
What are the three complex proteins of Troponin and what are their functions?
Troponin I = binds actin
Troponin T = Binds tropomyosin
Troponin C = binds calcium
Dystropin
Dystropin is a cytoskeletal element which links thin filaments to integral proteins of the sarcolemma, through a complex cytoskeletal structure called a costamere
What is tropmyosin?
covers active site on actin. Stabilizes and strengthensActin.(bike chain)
Functions of skeletal muscle
Produces movement
Maintains posture and body position
Maintains body temperature
Protects and supports soft tissue
Forms valves at openings
Neuromuscular junction
Site of communication between a motor neuron and muscle fibre
What parts of a contraction is chemical communication required?
1- across synaptic cleft (ACh)
2- Within sarcoplasm (Ca2+)
Describe steps fo excitation- contraction coupling simply.
Na iniates AP along sarcolemma and T Tubules
Voltage Gated receptors triggered releasing Ca from SR into cytosol
Ca binds to Troponin
Troponin changes shape as it removes blocking action of tropomyosin and exposes active sites
Contraction: myosin heads alternatively attach to actin and then detach = actin filaments pulled towards center
ATP energy powers process
What are the key steps for muscle relaxation?
NMJ stimulation ends.
AChe rapidly degrades ACh which is recycled by nerve terminal
Repolarization de-activates DHP-Rs and RYRs
Ca re-sequestered into SR
Troponin – tropomyosin complex reorientates so it covers active site.
Describe the interactions of Ca in the troponin-tropomyosin complex.
Ca binds to TRC of troponin complex
4 calcium = alters troponin complex (pulls tropomyosin away)
What are the two types of smooth muscle? List their characteristics.
Multiunit
Discrete cells that operate independently
Innervated (supplied with nerves) by motor neurons
Slow contraction
Single Unit
Act as a single unit
Gap junctions allow for AP and ion transmission
What are some unique features of Smooth muscle?
Thin filaments attached to dense bodies
Intermediate filaments (desmin) anchor actin and tropomyosin in thin
Scattered myosin when muscle relaxed.
What are the steps in Smooth Muscle contraction?
Voltage gated L-type Ca allows influx
Ca binds to Calmodulin (CaM)
CaCaM activates Myosin light chain kinase (MLCK)
MLCK phosphorylates MLC on myosin head = increased ATPase
Phosphorylated myosin polymerize (form a polymer) into thick filaments = forms cross-bridges
Cross-bridge cycling = dense bodies pulled towards each other
What are the steps of Smooth muscle relaxation?
VG Ca closes
Re-sequestration of Ca by SERCA
Ca concentration decreases = inactivates CaM and MLCK
MLCP dephosphorylates MLC = Thick filaments depolymerize
Smooth muscle relaxed.
What does smooth muscle contraction depend on?
Activation of MLCK by increased [Ca] intracellular
Why can smooth muscle contractions be maintained for prolonged periods without fatiguing?
Low energy demand (cross bridge last longer)
Slow onset of contraction and relaxation (Ca channel open for longer)
Slow Cross bridge cycling (little excitation to maintain contraction as cross-bridge detachments is slow)
What are points of difference between Smooth muscle and Skeletal muscle contractions?
thin filament attachment (dense bodies vs z-line)
Active site availability (always vs when [Ca] high)
myosin formation (scattered as a single molecule when relaxed vs always polymerised as thick and bound to M line)
influence of increased intracellular Ca on myosin (myosin polymerises into thick vs myosin always thick as long as ATP is present)
What are the 4-steps of cross bridge cycling
1- cross bridge formation
2- power-stroke
3- cross-bridge detachment
4-myosin heads rest
cross bridge formation
ATP binding pocket with mysoin ATPase in each myosin head
ATP hydrolyzed to ADP Pi which bind to myosin head
Re-cock and primes myosin head
power stroke
Contraction mechanism: when myosin to actin undergoes conformational change –> pulls actin towards center of sarcomere –> shortens sarcomere
What gets pulled towards the M-line in the power stroke?
thin filament and z-disc
What is released before and afetr the power stroke?
before = Pi
after = ADP
cross-bridge detachment
Binding of ATP to myosin head breaks cross-bridge
Importance: no more energy so cannot move any further.
mysoin heads rest
ATP hydrolysis recocks head in high energy conformation
Mysoin head primed until active site of actin exposed.
what do we call the posysynaptic membrane of the neuromuscular junction
Motor end plate
How is the neurotransmitter inactivated in synaptic cleft?
AChE
-breaks down ACh by terminated the action of ACh after released.
How does AChE regulate NM transmissiom?
By breaking down acetylcholine quickly, AChE helps ensure that muscle contraction is precisely controlled and that the muscle fiber does not remain in a state of constant contraction.
what happens to the I bind in skeletal muscle contraction?
shortens and reduces in width
what bands shorten in muscle contactions?
I band and H zone
What three events of NMJ require ATP?
Detachment of cross-bridges (binding of ATP)
Recocking myosin head (hydrolysis)
Reuptake of Ca into SR via SERCA (hydrolysis)
How do active sites on smooth differ from skeletal muscle fibres?
Smooth: Always available (no troponin)
Skeletal: Only available if intracellular Ca is elevated and troponin complex moves tropomyosin.
Describe myosin in Smooth vs skeletal muscle
Scattered as a single molecule when relaxed
Always polymerized, bound to M line
