Lecture 4 Flashcards
What are the three stages of excitation contraction coupling in regards to Ca2+?
- Ca2+ entry
- contraction
- relaxation/ Ca2+ uptake
How does Ca2+ enter the cell?
There is an action potential and the cell membrane depolarises. The membrane potential rises. The threshold of L-type Ca2+ channels is reached and these open. Ca2+ enters. This binds to the ryanodine receptor on the sarcoplasmic reticulum. This promotes further release of Ca2+ from the SR stores. The [Ca2+] in the cell increases hugely
Why is the calcium induced calcium release really efficient?
because the ryanodine receptor and L-type Ca2+ channel are really close in space so the diffusion distance is really small
What percentage of the calcium comes in via the L-type receptor and what percentage comes in via the ryanodine receptor from the SR?
25% from the L-type calcium receptor and 75% from the SR
In cardiac muscle, depolarisation causes what to happen?
Ca2+ induced Ca2+ release
How does Ca2+ drive contraction?
Ca2+ binds to troponin C in the troponin complex. Tropomyosin moves to allow an actin/myosin interaction and there is muscle contraction
What are the three troponin compounds that make up a troponin complex?
Troponin C
Troponin I
Troponin T
What is Troponin C?
This is the Ca2+ binding domain
What is Troponin I?
the inhibitory domain
What is Troponin T?
the tropomyosin binding domain
Briefly describe sarcomere shortening
Initially, the actin binding sites are blocked.
Ca2+ binds to the Troponin C. There is movement of the troponin/tropomyosin complex exposing the myosin binding site on actin. There is interaction between actin and myosin (cross-bridge).
The myosin head flips. The actin moves towards the centre of the sarcomere. The sarcomere shortens
When the sarcomere shortens, do actin and myosin also shorten?
no
Describe the cross-bridge cycle with relation to the ATP
- ADP + Pi is bound to the myosin head so myosin has a high actin affinity (but the troponin/tropomyosin complex is still blocking the site so they can’t bind)
- Ca2+ binds to TnC, there is movement of the troponin/tropomyosin complex exposing the myosin binding site on actin and now myosin can bind to the actin
- ADP + Pi is released which causes the myosin head to shift (90° to 45°) and the filaments slide over each other
- [Ca2+] decreases so it dissociates from TnC and so the troponin/tropomyosin complex rotates back to block the myosin binding site
- at the same time, ATP binds to myosin so myosin has a low actin affinity so the cross-bridge detaches
- myosin cleaves ATP to ADP + Pi and the process starts again
Describe the sliding filament theory
Myosin is pulling actin towards the centre of the sarcomere. Actin filaments slide along adjacent myosin filaments by cycling of cross-bridges with myosin. The Z line comes closer together and the cell shortens thus producing force or tension.
What percentage of myosin heads are needed to contract?
20%-40%