Skeletal muscle contraction

Question 1

excitation contraction coupling

Answer 1

where excitatory electrical signals are converted into mechanical contraction

Question 2

T tubules

Answer 2

AP propagates down T tubules and activates voltage gated L calcium channels a.k.a. dihydropyridine receptor

Question 3

triad

Answer 3

T tubule surrounded by terminal cisternae on either side

Question 4

terminal cisternae

Answer 4

the majority of SR calcium is stored in the terminal cisternae

here calcium is stored in its ionic form and bound to calcium binding protein calsequesterin

receptor ryanodine forms contact with 4 dihydropyridine receptors on the T tubule membrane

Question 5

SERCA pump

Answer 5

sarco endoplasmic reticulum calcium ATPases.

functions to transport calcium back into SR following calcium release across a large concentration gradient.

Question 6

calcium release from SR

Answer 6

when voltage gated calcium channels are activated they undergo a conformational change causing the dihydropyridine receptors to interact and activate ryanodine receptor in terminal cisternae causing a large release of calcium from the SR.

Question 7

A band

Answer 7

dark A band is composed of thick filaments of myosin that overlap with thin filaments (actin, troponin, tropomyosin)

Question 8

I band

Answer 8

light I band is composed of thin filaments ONLY anchored to the Z disc

Question 9

H zone

Answer 9

thick filaments ONLY

Question 10

Z disc

Answer 10

anchors thin filaments and titin filament

Question 11

titin filament/protein

Answer 11

titin gives structural stability for myosin and allows for elastic recoil

Question 12

M lines

Answer 12

centre of thick filament and provides structural stability and anchors myosin

Question 13

sarcomere

Answer 13

area between Z lines

Question 14

sliding filament theory

Answer 14

thin filaments slide over thick filaments towards the m line

A band remains constant
I band shortens
H zone shortens

Question 15

thin filament

Answer 15

G actin monomers polymerise to form F actin (filamentous)

2 F actin combine to form helix stabilised by protein nebulin

each G actin contains binding site for myosin

tropomyosin dimers block myosin binding site in the absence of calcium

tropomyosin binding is influenced by troponin complex

Question 16

troponin complex

Answer 16

troponin I = inhibits contraction by binding to actin and anchors tropomyosin to actin

troponin C = binds to calcium

troponin T = binds to tropomyosin and links the troponin complex to the tropomyosin dimer

Question 17

troponin complex and tropomyosin relationship

Answer 17

1 troponin complex exists for each single tropomyosin dimer

Question 18

myosin molecule (RHH)

Answer 18

rod = intertwined alpha helical heavy chains of myosin II protein forming a double helical structure

hinge = the rod myosin molecule flares into two globular heads

head region = S1 fragments each head contains 2 binding sites
one binding site for actin
one binding site for ATPase activity

Question 19

myosin light chains

Answer 19

hinge region has complex with 2 myosin light chains

MLC - 1 = essential/alkali light chain and stabilises the myosin head region influencing the kinetics of actin and myosin binding

MLC - 2 = regulatory light chain is critical for ATPase activity regulation. activity of MLC - 2 is regulated by phosphorylation of calcium dependent and calcium independent kinases.

Question 20

ATP hydrolyses

Answer 20

in the resting state ATP is partially hydrolysed by the myosin head to ADP + P and has a high affinity for actin in this state

following power stroke, energy of hydrolysed ATP is harnessed and ADP + P are released

binding of new ATP molecule to myosin head reduces the affinity for actin and the myosin head is released. ATP will be partially hydrolysed again ONLY IN THE PRESENCE OF CALCIUM

Question 21

timing of muscle contraction

Answer 21

can take 50 - 100 ms to peak.

AP peaks at 5 ms.

Calcium elevation begins after 20 ms.

AP lasts 2 - 5 ms whilst contraction response lasts > 100 ms.

Question 22

calcium removal following contraction

Answer 22

SERCA transporter or active transport out of the cell:
calcium hydrogen exchanger
sodium calcium exchanger.

Question 23

disturbances of calcium homeostasis

Answer 23

central core disease
brody’s disease
malignant hyperthermia

Question 24

malignant hyperthermia

Answer 24

triggered by anaesthetics halothane and causes a constant leak of calcium from the SR into the cytosol. Hyperthermia occurs when the body needs to constantly pump leaking calcium back into the SR. Causes muscle rigidity when leaking calcium binds with troponin C causing constant cross bridge formation.