Inherent Properties of Cardiac Muscle Flashcards
What is excitation contraction coupling?
the linking of the electrical excitability of a cell to its ability to generate force
Why are the issues when disease occurs in the heart?
ventricular myocytes do not divide and are not replaced
What are the features of cardiac muscle?
cannot fatigue
is enriched with large mitochondria
What is the sarcomere?
the single basic unit that the muscle is made up of
What is the distance between two Z disks?
2 microns
What is attached to the Z disk?
actin
What is the m-line?
the point where myosin is attached
Where are t-tubules found?
along the surface membrane diving down around the z-disks
What shape are ventricular myocytes?
brick shaped
Why are cardiac muscle fibres branched?
allows them to make contact with numerous neighbours
Why is the refractory period important?
prevents cardiac muscle from tetanising
protects against re-entrant arrhythmias
What prevents the heart from filling with blood properly?
any excitation outside the regular beat prevents the heart from filling with blood
What the three general states of most ion channels?
open
closed
inactivated
transition to the inactivated state is dependent on what?
time - the ion channel will inactivate after a certain amount of time
transition to the closed state is dependent on what?
voltage - it will happen when the membrane repolarises
What is unique about cardiac muscle compared to skeletal muscle?
it requires calcium to initiate contraction
What is the calcium transient?
the rise in IC Ca that gives rise to contraction after a delay
What is the resting Ca level?
100nM
What is the peak of Ca during a transient?
1uM
What are some of the properties of each dyad?
10-25 L-Type Ca channels
100-200 RyRs
What is a dyad?
the structure where the t-tubule meets the SR in the myocyte Z line
How long does it take for Ca to rise in the cell?
30ms
How is Ca removed from the cytoplasm?
SR CaATPase (SERCA) and the sarcolemmal Na/Ca exchanger - RELAXATION
What aids the uniform and simultaneous release of Ca across the cell?
the t-tubule network
What are the 3 accessory proteins of Actin?
tropomyosin I, TnT, TnC
What is required to release the myosin head from actin?
ATP
What happens in the absence of ATP?
myosin head remain attached and form rigor bonds
What does Ca do to allow contraction?
binds TnC
What does Ca binding TnC do?
changes the conformation pulling the tropomyosin out of the groove between actin filaments
exposes myosin binding site
What does the continued cycle with ATP, Ca, Myosin and Actin do?
pulls the sarcomere together
What is the state of TnI, TnC and Actin at rest?
TnC weakly interacts with TnI
TnI strongly interacts with Actin
troponin/Tropomyosin complex blocks myosin/actin interaction
What is the state of TnI, TnC and Actin in the presence of Ca?
TnC interacts with TnI and destabilised interaction with actin
Removes steric hindrance to actin-myosin
activates the ATPase activity of myosin
How far to the filaments slide per cross-bridge cycle?
5-10nm
What is the length tension relationship?
the basis of the Frank-Starling Law of the Heart
- amount of force generated depends on the how stretched the muscle is
- the more stretched the muscle, the greater the force
What does increasing sarcomere length initially do?
facilitates the overlap between thick and thin filaments and increases the no. of cross-bridges that can form
What is the maximal length where the overlap between thick and thin filaments is facilitated?
2.25uM
what do changes in overlap account for in cardiac muscle?
20% of the increase of force over the physiological range of sarcomere lengths
what does increasing sarcomere length do?
increase Ca sensitivity and maximally activated force
What is the effect on Ca sensitivity mediated by?
an increase in sensitivity of TnC for Ca
What does increasing sarcomere length do?
increase cross-bridge overlap
increased Ca sensitivity of myofilaments
When increased cardiac frequency, what happens?
the SR content increases and the force of contraction increases
Why does the SR content increase with increased bpm?
- L-type channels open more frequently and thus there is more Ca per second
- some of the extra Ca is sequestered in the SR stores
- bigger stores = bigger Ca release = increased force
Why does the force-frequency relationship decrease in the failing heart?
down-regulation of SERCA
up-regulation of NcX
What are the effects of down-regulating SERCA and upregulating NCX?
more calcium is extruded from the cell between beats and less Ca going into the SR
What is isovolumic contraction?
where the volume is not changing but the pressure does not exceed that of the aorta so blood cannot move out the ventricles
What are the stages of the cardiac cycle?
- diastole - chambers fill with blood
- atrial systole - atria contract - blood enters ventricles
- isovolumic contraction
- bicuspid valve closes - 1st heart sound
- ventricular systole
- isovolumic relaxation - 65mls left in heart - can increase output if needed
- aortic valve closes - 2nd heart sound
When does the 1st heart sound occur on the ECG?
with the QRS complex
When does the 2nd heart sound occur on the ECG?
just after T wave
What is the average Stroke Volume?
70mls