Cardiac Contraction Flashcards
What do cardiomyocytes make up?
Branching myofibres
What does each myocyte contain?
Multiple rod-like cross branched strands that run the length of repeating sarcomeres
What are t tubules?
Invagination of the muscle cell membrane that penetrates into the centre of cardiac muscle cells
What does the cytoplasm between the myofibrils contain?
The single, centrally located nucleus, mitochondria and sarcoplasmic reticulum
What are sarcomeres?
Cause muscle contraction when the actin and myosin filaments move relative to each other
What is proportional to intracellular calcium?
Force of contraction
What are the 5 steps in cardiac muscle contraction?
- sodium channels open allowing sodium to enter and depolarise the cell
- voltage gated calcium channels open
- plateau phase calcium influx and calcium induced calcium release
- calcium channels close and potassium channels open fully allowing potassium to leave and repolarise the cell
- stable sodium/potassium pump when cell is at rest
Where would you find ryanodine receptors?
Intracellular calcium channels
What does troponin T bind to?
Tropomyosin
What does troponin I bind to?
Actin filaments
What does troponin C bind to?
Calcium
What does binding of calcium to troponin C lead to?
Conformational changes of tropomyosin and exposure of actin binding sites
How does the calcium concentration decrease in myocytes?
- action potential repolarises t tubules, and the voltage gated calcium channels and decreased calcium influx
- no calcium influx-> no calcium induced calcium release
- extrusion of calcium from cell by Na/Ca exchanger
- calcium uptake into sarcoplasmic reticulum via SR membrane
- calcium is taken into the mitochondria
What is intrinsic stretch a result of?
Increased pressure or volume
What is extrinsic control due to calcium conc rise a cause of?
Some pressure or volume but increased contractility
What are drugs needed for clinically?
To increase the contractility of the heart
What do sympathetic mimetic drugs do?
Increase the voltage gated calcium channel activity
What do cardiac glycoside drugs do?
Reduce calcium extrusion
What do positive ionotropes do?
Increase the strength of contraction
What do beta 1 adrenoreceptors induce?
Increased contractility
What does increased pKA lead to?
- increased calcium channel so higher calcium level and greater contraction
- increased potassium channel opening so faster repolarization and shorter action potential leads to a faster heart rate
- increased sarcoplasmic reticulum calcium ATPase, so uptake of calcium into storage by SR allowing fresh relaxation
- overall stronger faster contractions, same diastolic time to allow for filling with blood and coronary perfusion
Why are cardiac glycosides not used often now?
Side effects
What is digitoxins mechanism of action?
It inhibits the sodium potassium ATPase
- Na build up lowers the concentration gradient
- less calcium epulsion by sodium/potassium exchanger , so it is taken up into stores
What drugs are used in acute heart failure?
Dobutamine and dopamine
What drug is used in acute heart failure when taking beta blockers (and how does it work)?
Glucagon
Acts as a GPCR, stimulates Gs pathway, and increases cAMP and pKA activity
What is amrinone?
Phosphodiesterase inhibitor
