Skeletal muscle contraction Flashcards
excitation contraction coupling
where excitatory electrical signals are converted into mechanical contraction
T tubules
AP propagates down T tubules and activates voltage gated L calcium channels a.k.a. dihydropyridine receptor
triad
T tubule surrounded by terminal cisternae on either side
terminal cisternae
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
SERCA pump
sarco endoplasmic reticulum calcium ATPases.
functions to transport calcium back into SR following calcium release across a large concentration gradient.
calcium release from SR
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.
A band
dark A band is composed of thick filaments of myosin that overlap with thin filaments (actin, troponin, tropomyosin)
I band
light I band is composed of thin filaments ONLY anchored to the Z disc
H zone
thick filaments ONLY
Z disc
anchors thin filaments and titin filament
titin filament/protein
titin gives structural stability for myosin and allows for elastic recoil
M lines
centre of thick filament and provides structural stability and anchors myosin
sarcomere
area between Z lines
sliding filament theory
thin filaments slide over thick filaments towards the m line
A band remains constant
I band shortens
H zone shortens
thin filament
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
troponin complex
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
troponin complex and tropomyosin relationship
1 troponin complex exists for each single tropomyosin dimer
myosin molecule (RHH)
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
myosin light chains
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.
ATP hydrolyses
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
timing of muscle contraction
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.
calcium removal following contraction
SERCA transporter or active transport out of the cell:
calcium hydrogen exchanger
sodium calcium exchanger.
disturbances of calcium homeostasis
central core disease
brody’s disease
malignant hyperthermia
malignant hyperthermia
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.
