Cardiac Excitation-contraction Coupling Flashcards
Where are T tubules positioned and what do they do ?
They enter at the level of the a disks and they permeate deep into muscle tissue to synchronise the contraction of the tissue
What disks border the sarcomeres ?
Z disks
What are A bands made up of ?
Thick filaments consisting of myosin
What are I bands made up of ?
Thin filaments mainly composed of actin
Where are the thin filaments attached to and how are they arranged ?
Attached to a disk and are arranged in a hexagonal array
Where are the thick filaments attached to and how are they arranged ?
Attached to the M line and they are also in a hexagonal array
What protein is associated with actin and how is it arranged ?
Tropomyosin
Lies in groove made by the 2 coiled strands of actin
Each actin filament has repeating structure of 7 actin monomers polymerised together and then associated with this is one tropomyosin
What is the other protein associated with the actin-tropomyosin complex ?
Troponin
Occurs every 38.5nm along the complex
What is troponin made up of ?
Tn-C = binds calcium ions Tn-I = binds to actin to inhibit the binding of myosin to actin Tn-T = binds tropomyosin
How are the thick filaments arranged?
Heads protrude out to form cross bridges
Tails tethered to thick filaments
What does the T tubule contain ?
Extracellular fluid so it can take this fluid directly to the heart
What is the connection between the T tubule and the SR. ?
Dyad
Where are L type calcium channels(DHPR) located ?
In the walls of the T tubules
They are positioned directly above the SR calcium release channels
Explain the structure of ryanodine receptors ?
Have 4 fold symmetry
Calcium binds to them causing them to open
Enable an influx of calcium ions from SR into cell cytosol
What is the difference between the arrangement of ryanodine receptors in skeletal and cardiac muscle?
Skeletal - DHPR arranged in tetrads over RyRs - this is very ordered
Cardiac - same number of RyRs as in skeletal but they have less DHPRs and their arrangement is less ordered
What are the similarities between cardiac and skeletal muscle ?
Both striated
Interdigitating thick and thin filaments giving a and I bands
Both have regulatory proteins tropomyosin and troponin
Cross bridge cycle is identical
Differences between cardiac and skeletal muscle
T tubules wider in cardiac muscle- requires an extracellular calcium input as well as intracellular
In cardiac t tubules enter at z lines whereas in skeletal it occurs at a-I boundary
Cardiac Tn-C can bind 3 calcium ions whereas skeletal can bind 4 of which 2 of the sites can also bind magnesium
Mechanism of SR calcium release is different
Fewer DHPRs in cardiac
Explain the steps in cardiac excitation-contraction coupling
1- ap travels across membrane surface down t tubules causing depolarisation of t tubular membrane
2- once membrane potential reaches >40 mV L type calcium channels open
3- the L type calcium channels are opposite the SR calcium release channels and the influx of calcium causes calcium to be released from the SR
4- calcium interacts with the myofilaments
5- calcium binds to Tn-C causing cross bridge cycles to begin
Why in cardiac tissue do the DHPRs have to cause a slight influx of calcium ions before the release of calcium from the SR ?
Because there is no physical contact between the DHPRs and ryanodine receptors
In cardiac tissue what percentage of calcium comes from outside the cell ?
20%
Other 80% released from SR
How is calcium removed from the cytoplasm to stop contraction ?
1- SERCA-2 = calcium pumped back into SR by ATP dependent pumps
2- sodium-calcium exchanger (NCX)= calcium iOS. Removed
3- PMCA= calcium removed via sarcolemmal calcium ATPase
How is the 20% of extracellular calcium removed from the cell ?
18-19% by NCX
1-2% by sarcolemmal calcium ATPase
How does the NCX exchanger work ?
It uses 3 sodium ions to remove 1 calcium ion
This causes a 1+ flow into the cell making this electrogenic
Why does the sarcolemmal calcium ATPase only remove 1-2% of calcium ?
Because it has such a low turnover rate that relaxation by this method would take 1 minute for 1 beat
What happens to the troponin complex in the absence of calcium ?
It's relaxed Tropomyosin is bound to actin Tn-T bound to tropomyosin and Tn-I Tn-I binds strongly to actin - this covers actin-myosin binding site so cross bridge can't form Tn-c binds weakly to Tn-I
What happens to the troponin complex when calcium is present ?
Contraction occurs
Calcium binds to Tn-C
Changes binding of Tn-c binding to Tn-I into high energy state
Causes Tn-I to no longer bind to actin
This changes binding of Tn-I to Tn-t which changes Tn-t binding to tropomyosin and therefore binding of tropomyosin to actin
Tropomyosin moves further into groove of actin causing troponin complex to move out allowing myosin to bind
Explain the cross bridge cycle ?
1- ADP and Pi attached to myosin head in high energy configuration
2- the release of ADP and Pi causes the power stroke pushing actin filaments to centre of sarcomeres
3- ATP binds to myosin causing cross bridge to detach putting head in low energy config
4- ATP hydrolysis occurs so heads return to high energy state
