Skeletal Muscle Contraction
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What happens after motor nerve activation
Opening of voltage gatied sodium channels. Located at nodes of Ranvier. Depolarisation until nerve terminal. Release of transmitter, causing actin and myosin to interact and cell shortening.
What happens as the nerve terminal is polarised
Calcium channels open and influx of calcium. Vesicles of acetylcholine fuse to membrane. Acetylcholine released and binds to receptor, causing membrane depolarisation. (Nicotinic acetylcholine receptor). Two acetylcholine -> Alpha 1 subunit -> Opening of channel -> Rapid influx of sodium, passes down T tubule
Describe Snare proteins and vesicles mechanisms.
Vesicle pulled to membrane, fusion of two lipid bilayers (vesicle and cell membrane) by interaction of SNARE proteins Vesicle v-SNARE and synaptotagmin - Synaptotagmin has a calcium binding site. Sarcoplasmic membrane - Has two target snares, Syntaxin-1 and SNAP 25 Fusion of the vesicle - Content release occurs when a V snare meets a T snare and a snare pin is created. Calcium binds to synaptotagmin - Binds to phospholipids in the membrane, and inhibitiory effect on v-Snare is removed. Vesicle is clamped to the membrane, pulling it to the t-Snares, creating a snare pin pulling everything together.
Why is transmitter release calcium dependent
Calcium binds to synaptotagmin, releasing v-Snare inhibition, trap the T-snare, brought close together because synaptotagmin has higher affinity for phospholipid in membrane.
What do the two subunits of botulinum toxin do
1- binds to a glycoprotein to cholingergic neurones allowing toxin entry 2- produces cellular effects - cleaving of SNAP 25, synaptobrevin
How is botulinum toxin destroyed
Heating above 85 degrees celsius for more than 5 mins.
Summarise skeletal muscle contraction in steps (before actin myosin)
Neuronal action potential -> Calcium influx into nerve terminal -> Fusion of acetylcholine vesicles to release acetylcholine -> Activates nicotine acetylcholine receptor
T tubules
Folded in membrane intimate with calcium store Depolarisation sweeps downn T tubule system T tubule in the SR has two proteins, calcium release channel (YRY) In the tubule itself, dihydropyridine receptor
What does dihydropyridine receptor do
Inhibits calcium release channel. Excitation removes dihydropyridine receptor so calcium is released, allowing actin myosin to bind.
Which receptors release calcium after DHPR detects depolarisation
RyR1 and 2
Describe differences between skeletal v cardiac muscle with functional ion channel
Cardiac - Calcium induced calcium release (CICR) Skeletal - pHysical interaction between DHP and RyR
Describe structure of thin filament
Z-disk held by alpha actinin Actin, tropomyosin, and troponin (Calcium binding site and tropomyosin binding site)
Describe structure of thick filament
Made up of myosin Big strong, forms cross bridges Myosin head flexible and has ATPase, consumes ATP to generate power stroke
What happens when calcium binds to troponin
Increases affinity for troponin to tropomyosin, moving the tropomyosin away from the myosin binding site. This allows activated myosin to interact with the actin.
Describe the contractile cycle with ATP
ATP binds to myosin. It is hydrolysed to myosin + ADP, the head of the myosin flexes. If calcium removed, primed myosin interacts with actin. - Power stroke occurs, ADP released, myosin flexes towards centre of sarcomere. If another molecule of ATP comes, myosin detaches, restarting the cycle with ATP hydrolysis