The molecular mechanics of cardiac contraction Flashcards
main components of myocardium
contractile tissue, connective tissue,
fibrous frame,
specialised conduction system
what does the pumping action of the heart depend on?
pumping action of the heart depends on interactions between contractile proteins in its muscular walls
what do the interactions do?
interactions transform the chemical energy derived from ATP into the mechanical work that moves blood
how are contractile proteins activated?
signalling process called excitation-contraction coupling
when does excitation-contraction coupling begin and end?
begins when action potential depolarises the cell
ends when ionised calcium (Ca2+) that appears within the cytosol binds to the Ca2+ receptor of the contractile apparatus
movement of Ca2+ into cytosol
passive (downhill) process mediated by Ca2+ channels
when does the heart relax?
when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol
the working myocardial cell
filled with cross-striated myofibrils
plasma membrane regulates excitation-contraction coupling and relaxation
plasma membrane separates cytosol from extracellular space and sarcoplasmic reticulum
mitochondria for ATP, aerobic metabolism and oxidative phosphorylation
myocardial metabolism
aerobic and anaerobic metabolism
aerobic metabolism
relies on FFA during aerobic metabolism
anaerobic metabolism
no FFA metabolism during hypoxia
metabolising glucose
producing energy sufficient to maintain survival of affected muscle without contraction
myofibrils
contractile proteins arranged in a regular array of thick and thin filaments
bands/lines
A-band
I-band
Z lines
A-band
region of the sarcomere occupied by the thick filaments
I-band
is occupied only by thin filaments that extend toward the centre of the sarcomere from the Z-lines
contains tropomyosin and troponins
Z lines
bisect each I-band
what is the sarcomere?
functional unit of the contractile apparatus
region between a pair of Z-lines
contains 2 half I-bands and one A-band
what is the sarcoplasmic reticulum?
membrane network surrounding the contractile proteins
consists of sarcotubular network at centre of the sarcomere and the subsarcolemmal cisternae (T-tubules and sarcolemma)
transverse tubular system
T tubule
lined by membrane continuous with the sarcolemma, so the lumen of the t tubules carries the extracellular space towards centre of the myocardial cell
what happens in contraction?
sliding of actin over myosin by ATP hydrolysis through the action of ATPase in the head of the myosin molecule
what do the myosin heads do?
heads form crossbridges that interact with actin, after linkage between calcium and TnC, and deactivation of tropomyosin and TnI
what is myosin?
2 heavy chains also responsible for the dual heads
4 light chains
heads are perpendicular on thick filament at rest, and bend towards the centre of the sarcomere during contraction
what is actin?
globular protein
double stranded macromolecular helix (G|)
both form F actin
what is tropomyosin and what does it do?
elongated molecule
2 helical peptide chains
occupies each of the longitudinal grooves between the 2 actin strands
regulates interaction between other 3
types of troponin
I, T, C
troponin I
with tropomyosin it inhibits actin and myosin interaction
troponin T
binds troponin complex to tropomyosin
troponin C
high affinity calcium binding sites, signalling contraction
drives TnI away from actin, allowing its interaction with myosin
control of the contractile cycle
calcium ions
troponin phosphorylation
myosin ATPase
myosin location and salient properties
thick filament
hydrolyses ATP, interacts with actin
actin location and salient properties
thin filament
activates myosin ATP, interacts with myosin
tropomyosin location and properties
thin filament
modulates actin-myosin interaction
troponin C location and salient properties
thin filament
binds Ca2+
troponin I location and salient properties
thin filament
inhibits actin-myosin interaction
troponin T location and salient properties
thin filament
binds troponin complex to thin filament
Na+ channel role in excitation-contraction coupling
systole - depolarisation and open Ca2+ channels
Ca2+ channel role in excitation-contraction coupling
systole - action potential plateau and Ca2+ triggered Ca2+ release
Ca2+ pump (PMCA) role in excitation-contraction coupling
diastole - Ca2+ removal
Na+/Ca2+ exchanger roles in excitation-contraction coupling
systole - Ca2+ entry
diastole - Ca2+ removal
Na+ pump role in excitation-contraction coupling
diastole - repolarisation
and Na+ gradient for Na+/Ca2+ exchange
Subsarcolemmal cisternae Ca2+ release channel role in excitation-contraction coupling
systole - Ca2+ release
sarcotubular network’s Ca2+ pump (SERCA)
diastole - Ca2+ removal
actin and myosin role in excitation-contraction coupling
systole - contraction
troponin C role in excitation-contraction coupling
systole - Ca2+ receptor
size of cardiac muscle cells
100um long and 20um diameter
how are adjacent cardiac cells joined together?
end to end at intercalated disks - desmosomes join cells together, myofibrils attached to them. gap junctions also within them.
how are cardiac muscle cells arranged?
in layers
surround hollow cavities
depolarisation and Ca2+
influx of Ca2+ through specialised voltage-gated channels (L-type Ca2+ channels) - modified versions of dihydroxypiridine (DHP) receptors.
triggers release of larger amount of Ca2+ from sarcopasmic reticulum
why is the release of Ca2+ from the SR triggered?
ryanodine receptors in the cardiac SR terminal cisternae are Ca2+ receptors
not opened directly by voltage channels, but by the binding of trigger Ca2+ in the cytosol
when does contraction end?
when cystolic Ca2+ concentration is restored to its original low resting value by primary active Ca2+ -ATPase pumps in the SR and sarcolemma and Na+/Ca2+ countertransporters in the sarcolemma
Ca2+ exits the cell and returns to the SR via pumps, and K+ exits the cell and repolarises the membrane
