MSS- muscle contraction mechanisms

Question 1

outline the roles of muscles

Answer 1

movement - walking, running
hollow organ movement - heart, bv, GI
structure - chambers of the heart etc..

Question 2

what type of control are muscles under

Answer 2

both voluntary and involuntary

Question 3

what is the difference between striated and smooth muscle in terms of actin and myosin organisation

Answer 3

smooth - disorganised actin and myosin

skeletal - organised actin and myosin (hence the striations)

Question 4

how are the skeletal muscles controlled

Answer 4

motor nerves - controlled by the brain

Question 5

how are smooth muscles controlled

Answer 5

ANS

Question 6

why is unorganised actin / myosin good for smooth muscle

Answer 6

creates contractions from all dimensions

Question 7

describe actin

Answer 7

globular protein (G actin) , binds ATP and contains ATPase activity which hydrolyses ATP into ADP and inorganic phosphate

this energy forms chains for G actin to make a helical protein (F actin) which contains active actin binding sites allowing interactions with myosin

Question 8

describe myosin

Answer 8

2 heavy chains, 4 light chains, 2 heavy chains are intertwined producing N terminal head domains which bind to actin

these head domains bind ATP and ADP and contain ATPase activity

Question 9

where is tropomyosin found

Answer 9

striated muscle

Question 10

what is the function of tropomyosin

Answer 10

wraps around acting which covers the active actin binding sites at rest

this means that actin and myosin wont come together at rest

troponin system - TnI, TnC, TnT

Question 11

how is muscle contraction initiated

Answer 11

rise in Ca inside muscle cells

increase in calcium leads to the removal of tropomyosin from the actin binding sites

therefore exposed sites are able to attach to myosin

Question 12

how is a rise in calcium produced

Answer 12

extracellular concentration of Ca - 1-2 mM
intracellular concentration of Ca - 100nM

calcium stored in SR and diffusion from outside the cells increases Ca in cytoplasm removing tropomyosin

Question 13

describe the action of myosin during contraction

Answer 13

ATP binds to myosin heavy chain heads - low affinity for actin binding

hydrolysis of ATP at myosin heads means they become energised and oriented - high affinity for actin binding sites

interaction between actin and myosin releases a phosphate molecule which allows binding

the myosin binds to the actin forming cross bridges

Question 14

outline the sliding filament hypothesis

Answer 14

after myosin / acting binding

90degree cocking motion where ADP is released - more energy to reaction

a 45 degree cocking motion is then produced between actin and myosin

acts like a rowing motions - causes a shortening between the sarcomeres

myosin cross bridges rotate towards the centre of the sarcomere - power stroke

as ADP is now absent the myosin comes away from the actin binding site - allowing the cycle to start again

Question 15

what is rigor mortis

Answer 15

a consequence of the sliding filament hypothesis

myosin heads need to be constantly primed with ATP to be ready for contraction

Question 16

what is the process behind rigor mortis

Answer 16

needs ATP for myosin binding and for detachment of myosin - actin

in death:

increase in calcium = removal of tropomyosin from actin
loss of ATP production prevents detachment of actin - myosin filaments - causes the stiffness of muscles
starts 2-6 hours after death - peaks at 12 hours)

stops at 24-48 hours due to decomposition of myosin / actin proteins

Question 17

explain how a rise of calcium allows the uncovering of actin binding sites by tropomyosin

Answer 17

TnT - binds to tropomyosin
TnI- binds to actin sites
TnC- binds to calcium

calcium binds to TnC
causing a conformational change of the TnT/TnI tropomyosin complex
leads to the exposure of actin active sites allowing the myosin to bind and the initiation of the sliding filament hypothesis

Question 18

describe the activation of nicotinic ligand gated receptors in skeletal muscle

Answer 18

activation by Ach (released by motor nerves)

Ach binds to alpha subunit of ligand receptors - allows sodium into the cell

Question 19

how are nicotinic receptors activated at the NMJ

Answer 19

conduction of action potential in the motor nerves

causes voltage gated calcium channels to open causing calcium influx and the formation of Ach vesicles

these vesicles (due to calcium) bind the the cleft and release into the synapse

move along the concentration gradient and bind to alpha subunit of the nicotinic receptor

this activation brings sodium into the skeletal cell

the influx of sodium causes depolarisation which activated the voltage gated calcium channels - contraction

breakdown of Ach by AchE = termination of response - choline recycled into the neurone and acetyl CoA is washed out

Question 20

how is skeletal muscle contracted

Answer 20

action potential is conducted through skeletal muscle via t-tubules

the action potential opens voltage gated calcium channels with have a direct connection with the ryr of the SR

ryr allows stored calcium to go into the cytoplasm where it increases calcium level and allows binding of actin and myosin

Question 21

outline how stimulation of beta 1 adrenoreceptors increases contractility of cardiac muscle

Answer 21

electrical activity generated in SAN

action potential stimulates the opening of VGCC which allows calcium into the cell

not directly linked with the SR

calcium induced calcium release

triggers contraction

activation of beta 1 adrenoreceptors
(gs)

stimulation converted ATP to cAMP (intracellular messenger)
cAMP production triggers PKA, whcih phosphorylates VGCC and ryr receptors

causes more VGCC to open = increase in Ca influx

PKA stimulates ryr receptor = calcium release

= increased contraction

Question 22

how do you produce relaxation in muscle

Answer 22

lower Ca inside the cell using CAATPase and using sodium exchanger

CAATPase transport calcium into storage - against concentration gradient

a decrease in Ca causes a reduced TNC Ca binding, therefore leading to tropomyosin to bind back onto actin binding sites - preventing interaction

Question 23

where is smooth muscle found

Answer 23

walls of tubular organs - blood vessels, GI tract, airways, uterus, bladder, eye

Question 24

what are the characteristics of smooth muscle contraction

Answer 24

slow, sustained, graded
relative weak
innervated by ANS
can have myogenic contractions
excitable cells produce action potentials like skeletal muscle and cariad muscle

Question 25

what transmitters released from post-ganglionic autonomic nerves act on smooth muscle cells

Answer 25

acetyl choline - parasympathetic
noradrenaline - sympathetic
nitrous oxide- NANC

Question 26

how is smooth muscle contraction mediated

Answer 26

action potential 
VGCC open allowing Ca influx
Ca influx stimulates g proteins
stimulated G protein (gq) generates IP3
IP3 travels through the cell and binds to IP3 receptors in SR which causes the release of Ca into the cytoplasm - causing contraction event

Question 27

how is relaxation in smooth muscle achieved

Answer 27

calcium calmodulin phosphorylates MLCK to produce contraction

MLC-phosphatase dephosphorylates MLC

hyperpolarisation of the cell by VGKC allows K out of the cell = hyper negative polarisation forcing the closure of the VGCC
CAATPase causes uptake of calcium into SR
Na/Ca exchanger excludes calcium from the cell