Cardiac Excitation-contraction Coupling

Question 0

Where are T tubules positioned and what do they do ?

Answer 0

They enter at the level of the a disks and they permeate deep into muscle tissue to synchronise the contraction of the tissue

Question 1

What disks border the sarcomeres ?

Answer 1

Z disks

Question 2

What are A bands made up of ?

Answer 2

Thick filaments consisting of myosin

Question 3

What are I bands made up of ?

Answer 3

Thin filaments mainly composed of actin

Question 4

Where are the thin filaments attached to and how are they arranged ?

Answer 4

Attached to a disk and are arranged in a hexagonal array

Question 5

Where are the thick filaments attached to and how are they arranged ?

Answer 5

Attached to the M line and they are also in a hexagonal array

Question 6

What protein is associated with actin and how is it arranged ?

Answer 6

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

Question 7

What is the other protein associated with the actin-tropomyosin complex ?

Answer 7

Troponin

Occurs every 38.5nm along the complex

Question 8

What is troponin made up of ?

Answer 8

Tn-C = binds calcium ions 
Tn-I = binds to actin to inhibit the binding of myosin to actin 
Tn-T = binds tropomyosin

Question 9

How are the thick filaments arranged?

Answer 9

Heads protrude out to form cross bridges

Tails tethered to thick filaments

Question 10

What does the T tubule contain ?

Answer 10

Extracellular fluid so it can take this fluid directly to the heart

Question 11

What is the connection between the T tubule and the SR. ?

Answer 11

Dyad

Question 12

Where are L type calcium channels(DHPR) located ?

Answer 12

In the walls of the T tubules

They are positioned directly above the SR calcium release channels

Question 13

Explain the structure of ryanodine receptors ?

Answer 13

Have 4 fold symmetry
Calcium binds to them causing them to open
Enable an influx of calcium ions from SR into cell cytosol

Question 14

What is the difference between the arrangement of ryanodine receptors in skeletal and cardiac muscle?

Answer 14

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

Question 15

What are the similarities between cardiac and skeletal muscle ?

Answer 15

Both striated
Interdigitating thick and thin filaments giving a and I bands
Both have regulatory proteins tropomyosin and troponin
Cross bridge cycle is identical

Question 16

Differences between cardiac and skeletal muscle

Answer 16

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

Question 17

Explain the steps in cardiac excitation-contraction coupling

Answer 17

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

Question 18

Why in cardiac tissue do the DHPRs have to cause a slight influx of calcium ions before the release of calcium from the SR ?

Answer 18

Because there is no physical contact between the DHPRs and ryanodine receptors

Question 19

In cardiac tissue what percentage of calcium comes from outside the cell ?

Answer 19

20%

Other 80% released from SR

Question 20

How is calcium removed from the cytoplasm to stop contraction ?

Answer 20

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

Question 21

How is the 20% of extracellular calcium removed from the cell ?

Answer 21

18-19% by NCX

1-2% by sarcolemmal calcium ATPase

Question 22

How does the NCX exchanger work ?

Answer 22

It uses 3 sodium ions to remove 1 calcium ion

This causes a 1+ flow into the cell making this electrogenic

Question 23

Why does the sarcolemmal calcium ATPase only remove 1-2% of calcium ?

Answer 23

Because it has such a low turnover rate that relaxation by this method would take 1 minute for 1 beat

Question 24

What happens to the troponin complex in the absence of calcium ?

Answer 24

``` 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 ```

Question 25

What happens to the troponin complex when calcium is present ?

Answer 25

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

Question 26

Explain the cross bridge cycle ?

Answer 26

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