cardiac contraction Flashcards
give the structure of cardiomyocytes
- 60–140 μm in length and 17–25 μm diameter make up the branching myofibres.
- Each myocyte contains multiple, rod-like cross-banded strands (myofibrils) that run the length of the cell and are composed of repeating sarcomeres.
*Cytoplasm between the myofibrils contains the single centrally located nucleus, mitochondria, and sarcoplasmic reticulum (intracellular membrane system).
give the structure of T tubules
- are invaginations of the muscle cell membrane (sarcolemma) that penetrate the centre of cardiac muscle cells.
give the structure of sarcomeres
- cause muscle contraction when their component actin and myosin filaments move relative to each other.
- The varying actin myosin overlap is shown for systole (contraction) and diastole (relaxation).
give an overview of cardiomyocyte function
The T tubules (invaginations of the membrane) have calcium channels and ensure calcium is delivered deep into the cell close to the sarcomere.
Ca2+ enters via calcium channel that open in response to the wave of depolarization that travels along the sarcolemma where they trigger the release of more calcium from the sarcoplasmic reticulum and initiate contraction.
The varying actin-myosin overlap is shown for systole, when [Ca2+] is maximal, and diastole, when [Ca2+] is minimal.
Eventually the Ca2+ that has entered the cell leaves predominantly through an Na+/Ca2+ exchanger.
describe the rise in intracellular calcium in order to cause contraction
Action potential (Na+ ions) depolarises T-tubules & activates VGCCs causing Ca2+ influx
Ca2+ binds to RyR located on the sarcoplasmic reticulum (SR) - close association with T-tubules
Release of Ca2+ from SR - Ca induced Ca release (CICR)
Ca2+ binds to troponin, displacement of tropomyosin/troponin complex, exposing active sites on actin
Myosin thick filament heads bind to active sites on actin & filaments slide (using ATP)
how does electrical excitability contract cardiac myocytes ?
Contraction is determined by INCREASE in [Ca2+]i
Higher increases in Ca2+ → increased force of contraction
Intracellular Ca2+ levels increase from 0.1 µM to about 10 µM
what are the 3 components of troponin ?
T - binds to tropomyosin - blood plasma markers for cardiac cell death
I - binds to actin filaments - blood plasma markers for cardiac cell death
C - binds Ca2+ - leads to conformational changes of tropomyosin and exposure of actin binding sites.
describe the contraction cycle
describe the decrease in calcium which leads to relaxation
Action potential repolarisation (K+ ions leave) repolarises T-tubules – closure of VGCCs, and less Ca2+ influx.
No Ca2+ influx, no calcium induced calcium release
Extrusion of Ca2+ from cell (30%)- by Na+/Ca2+ exchanger.
Ca2+ uptake into sarcoplasmic reticulum (SR) via SR membrane Ca2+ATPase (around 70%).
Ca2+ in SR for next contraction, even relaxation requires energy (ATP).
Uptake of Ca2+ in mitochondria.
what is the difference between starlings law and contractility ?
Starling’s Law describes the relationship between filling volume and contraction force, while contractility is the inherent strength of that contraction regardless of filling volume
what are inotropes ?
drugs that change the force of a heart’s contractions.
how does the sympathetic nervous system control cardiac contractility ?
Noradrenaline (NA) acts via b1-adrenoceptors to increase contractility by phosphorylating calcium channels and allowing greater Ca2+ influx and higher intracellular levels
what does increased PKA lead to ?
Increased Ca2+ channel so higher Ca2+ levels and greater contraction.
Increased sarcoplasmic reticulum Ca2+ATPase, so uptake of Ca2+ into storage by SR allowing faster relaxation.
Increased K+ channel opening so faster repolarisation and shorter action potential, leads to faster heart rate.
Overall stronger faster contractions but same diastolic time to allow for filling with blood & coronary perfusion.
what are cardiac glycosides ?
a class of drugs that treat heart failure and certain irregular heartbeats
describe the mechanism of action of digoxin
Digoxin inhibits Na+/K+ ATPase.
Build up of intracellular Na+ lowers concentration gradient (which normally powers Na+/Ca2+ exchanger).
Less Ca2+ expulsion by Na+/Ca2+ exchanger.
More Ca2+ uptake into stores and greater CICR
what are the side effects of digoxin ?
- tiredness and fatigue
- anxiety
- hallucinations
describe some other intropic agents
Dobutamine & dopamine are 1-adrenoceptor stimulants - may be used in acute heart failure.
Glucagon – acts at G protein coupled receptor, stimulates GS pathway, increases cAMP and PKA activity. Used in patients with acute heart failure who are taking β-blockers.
Amrinone – a phosphodiesterase inhibitor
