Term
Is the architecture of cardiac muscle similar to skeletal muscle? |
|
Definition
Yes. They are both made up of the same repeating units (sarcomeres) which are bordered by the Z-discs, incorporating myofibrils, SR, t-tubules, mitochondria and nuclei. |
|
|
Term
|
Definition
contains thick filaments which are mainly composed of the protein myosin |
|
|
Term
|
Definition
contains thin filaments which are mainly composed of the protein actin |
|
|
Term
How are the thin and thick filaments arranges? |
|
Definition
Thin filaments are attached to te Z-discs and are arranged in a hexagonal array.
Thick filaments are organised by the M-line - also in a hexagonal arrangement. |
|
|
Term
What is the role of titin? |
|
Definition
Titin is associated with thick filaments, it imparts series elasticity and is anchored by the Z-discs. |
|
|
Term
Describe the thin filament structure |
|
Definition
- Actin filament has a double stranded rope-like structure. - Long protein tropomyosin lies in the groove made by 2 actin strands - Each strand of the actin filament has a repeating structure composed of 7 actin monomers polymerised together and associated with one tropomyosin protein units. |
|
|
Term
What is the troponin complex? |
|
Definition
situated 38.5nm along the actin-tropomyosin filament there is another protein complex called troponin. The complex is made up of 3 subunits: Troponin-C, Troponin-I and Troponin-T. |
|
|
Term
|
Definition
moleculare weight: 18000 role: binds Ca2+ ions to produce a conformational change in Troponin 1 |
|
|
Term
|
Definition
molecular weight: 25000 role: binds to actin. It's role is to inhibit the binding of myosin to actin |
|
|
Term
|
Definition
molecular weight: 42000 role: binds to tropomyosin, interlocking them to form a troponintropmyosin complex |
|
|
Term
Describe the thick filament structure |
|
Definition
- Each myosin molecule is tethered to the thick filament by its tail with the head sticking out. - Each thick filament is at the centre of a hexagonal array of thin filaments - made up of 300 individual myosin molecules packed together |
|
|
Term
Describe the head of the thick filament |
|
Definition
2 individual subunits known as crossbridges site of ATP hydrolysis and consequent tension generation |
|
|
Term
|
Definition
- they invaginate muscle fibres at the level of the Z-line - they are continuous with the surface membrane (sarcolemma) of the muscle fibre and contain ECF. |
|
|
Term
How is the saroplasmic reticulum (SR) related? |
|
Definition
- made up of longitudinal and terminal elements - terminal cisternae of SR are located very closely to the tubules (crucial for ECC in cardiac muscle) - acts as a calcium store!! |
|
|
Term
What is the outside face of the SR decorated with? |
|
Definition
SR Ca2+ release channels (ryanodine receptors - RYRs) |
|
|
Term
Which channels are located in the wall of the t-tubule? |
|
Definition
L-type Ca2+ channels (DHPR) they are situated directly over the SR Ca2+ release channels |
|
|
Term
How does the RYR/DHPR arrangement differ from skeletal to cardiac muscle? |
|
Definition
skeletal: DHPRs are arranged in tetrads over a RYR cardiac: fewer DHPRs and arrangement is less systematic (almost random with respect to RYRs) |
|
|
Term
List the similarities between cardiac and skeletal muscle (4) |
|
Definition
1. both are striated 2. interdigitating thin and thick filaments giving characteristic A and I bands 3. Thin filament regulatory proteins such as tropomyosin and troponin are present in both muscle types. 4. identical cross bridge cycle |
|
|
Term
List and explain the differences between cardiac and skeletal muscle regarding t-tubules |
|
Definition
1. T-tubules wider in cardiac muscle (reduces ionic depletion) 2. T-tubules enter the cells at Z-lines in cardiac muscle and A-I boundary in skeletal muscle |
|
|
Term
List and explain the differences between cardiac and skeletal muscle regarding Ca2+ |
|
Definition
1. Cardiac troponin-C can ony bind 3 Ca2+ ions compared to 4 for skeletal muscle (two of these sites can also bind Mg2+) 2. Mechanism of SR Ca2+ release is different |
|
|
Term
Any other differences between cardiac and skeletal muscle? |
|
Definition
Fewer DHPRs in cardiac muscle |
|
|
Term
What is required for RYRs to open in cardiac muscle? |
|
Definition
Ca2+ must enter through L-type Ca2+ channels to cause the RYRs to open. Hence the name 'calcium-induced calcium release'. |
|
|
Term
Describe the Cardiac Excitation-Contraction Coupling Mechanism |
|
Definition
1) AP travels across the surface membrane of the ventricular cell and down the t-tubules. 2) This will depolarise the t-tubular membrane where the L-type Ca2+ channels (DHPRs) are concentrated 3) Ca2+ channels in SR membrane situated directly opposite t-tubules are Ca2+ release channels (the RYRs). The RYRs and SHPRs are coupled together and physically link the t tubules and SR membranes 4) Ca2+ entry through L-type channels cause SR Ca2+ release channels to open and Ca2+ floods out of the SR into the cytoplasm. |
|
|
Term
What induces membrane depolarisation? |
|
Definition
opening of Na+ channels which underlies the upstroke of the AP |
|
|
Term
What does this tell us about where the Ca2+ required for contraction comes from? |
|
Definition
A small amount of Ca2_ crossing the cell membrane via Ca2+ channels causes a larger amount of Ca2+ to be released from the SR.
20% of the Ca2+ for each contraction comes from outside the cells with the remaining 80% released from the SR. |
|
|
Term
How does relaxation occur? |
|
Definition
Ca2+ must be removed from the cytoplasm by one of three pathways |
|
|
Term
List the 3 pathways in which Ca2+ is removed so relaxation can occur |
|
Definition
1. Ca2+ pumped back into the SR by ATP-dependent Ca2+ pumps. 2. Ca2+ is removed from the cell via Na/Ca exchanger 3. Ca2+ is removed from the cell via sarcolemma Ca2+ ATPase |
|
|
Term
What is the fate of Ca2+ removed for relaxation? |
|
Definition
80% returned to the SR. 20% leaves the cell: 18-19% via the NCX and 1-2% via the sarcolemmal ca2+ ATPase. |
|
|
Term
Describe the events that follow activation of heart muscle cells via the AP |
|
Definition
- rise of Ca2+ in the cytoplasm - Ca2+ binds to troponin-C which acts as a molecular switch to allow cross bridge cycling to occur. |
|
|
Term
How is a steady state level of Ca2+ in cells maintained? and why? |
|
Definition
The NCX uses the power of the inwardly directed electro-chemical gradient for Na+ to extrude Ca2+ from the cell against its concentration gradient (not an active process).
The amount of Ca2+ that entered during excitation has to be removed from th cell before the next beat. |
|
|
Term
How many Na+ ions does it take to remove of Ca2+ ion? |
|
Definition
|
|
Term
What does it mean that NCX is electrogenic? |
|
Definition
generates electricity in living tissues/organisms |
|
|
Term
Why isn't the sarcolemmal Ca2+ ATPase efficient enough? |
|
Definition
It is a high affinity pump but has a slow turnover rate in comparison. Relaxation of a single beat using this mech would take almost 60s. |
|
|
Term
How does binding of Ca2+ to troponin C initiate contraction? |
|
Definition
When Ca2+ binds to Tn-C, this initiates a series of changes in protein-protein interactions and eventually allow cross-bridge cycling to occur |
|
|
Term
Describe the troponin complex in a relaxed state (absence of calcium) |
|
Definition
- tropomyosin is bound to actin filament - Tn-T is bound to tropomyosin and Tn-I - Tn-I strongly bound to actin - Tn-C is bound weakly to Tn-I |
|
|
Term
What is the significance of Tn-I being strongly bound to actin? |
|
Definition
this blocks the actin-myosin binding site therefore myosin cannot bind to actin |
|
|
Term
How does the troponin complex change in the active state? |
|
Definition
1) calcium levels rise in the cytoplasm and binds to Tn-C 2) Tn-C binds more strongly to Tn-I 3) Tn-I can no longer bind to actin |
|
|
Term
What follows Tn-I being no longer able to bind to actin? |
|
Definition
a change in the binding of Tn-I to Tn-T and subsequent changes in the binding of Tn-T to tropomyosin and tropomyosin to actin. |
|
|
Term
What causes the actin binding site to be uncovered? |
|
Definition
- tropomyosin molecules moving further into the groove of the actin filament - myosin site on actin is uncovered and the myosin cross bridge can now bind actin |
|
|
Term
What happens if calcium is lowered again? |
|
Definition
Ca2+ dissociate from Tn-C, Tn-I will bind once again to actin and the myosin binding site will be blocked. |
|
|
Term
Describe the myosin head in a resting sarcomere |
|
Definition
- each head is energised and charged with the energy that will be used to power a contraction. - each head points away from the M line (cocked) |
|
|
Term
What causes a myosin head to cock |
|
Definition
energy!! obtained by breaking down ATP the myosin head functions as ATPase at the start of contraction, the breakdown products (ADP and phosphate) remain bound to the myosin head. |
|
|
Term
What happens once the active sites on actin are exposed? |
|
Definition
the energised myosin heads bind to them forming cross-bridges and energy stored in resting state is released as myosin heads pivot towards the M line. POWER STROKE ADP and P released. |
|
|
Term
How does the cross bridge become detached? |
|
Definition
another ATP binds to the myosin head, the link between the myosin head and the active site on actin is broken.
active site is now exposed. |
|
|
Term
How is the actin reactivated? |
|
Definition
when the free myosin head splits ATP into ADP and P. The energy released is used to cock the head. |
|
|