Cardiac Contraction Flashcards
What is a myocyte made up of
Myofibrils which contain sarcomeres
(sarcomeres are units containing actin + myosin needed for muscle contraction)
Sarcolemma is the cell membrane around myofibrils
Outline the events pre muscle contraction in terms of T-tubules
1) T-tubules invaginate cell membrane/sarcolemma
2) they connect outside of cell to inside
3) T-tubules contain Ca2+ channels and transmit Ca2+ to sarcomere
4) Ca2+ from T-tubules bind to RyR found on SR (calcium store)
5) CICR
6) Ca2+ binds to troponin…muscle contraction
What is the minimum concentration of Ca2+ required for muscle contraction
1um
Explain intracellular rise in calcium concentration
- action potential depolarises atrial or ventricular myocytes
- T-tubules are also depolarised by Na+ ions
- this opens VGCaC causing Ca2+ influx
- Ca2+ binds to RyR on SR
- Ca2+ binds to troponin, tropomyosin moves, exposing actin binding site (conformational change)
- Myosin head binds to actin site forming a cross bridge
- Myosin head ATPase activity releases energy
cycle continues until Ca2+ levels drop and Ca2+ dissociates from troponin, tropomyosin moves back into original position blocking binding site
What are the 3 subunits in troponin and their function
Troponin C: Ca2+ binds to TnC
Troponin T: binds to tropomyosin causing it to move/conformational change
Troponin I: binds to actin filaments
What is a good indicator of heart attack (MI)
TnT and TnI are released into bloodstream during a heart attack
How is calcium removed from a cardiac myocyte during relaxation
1) Sodium-Calcium exchanger removes 30% of Ca2+ from cell
2) Calcium ATPase transports 70% of Ca2+ into SR. Protein Kinase A increases Calcium ATPase activity.
3) small amount of calcium is taken up into mitochondria
Name 2 drugs used to treat bradycardia by increasing contractility of heart / increase concentration of Ca2+
Dopamine (sympathetic mimetic)
Digitalis (cardiac glycosides)
How do cardiac glycosides increase contractility of the heart
- reduce Ca2+ removal
- inhibit Sodium-Potassium ATPase
- sodium (alongside Ca2+) are no longer able to be pumped out of cell
- more Ca2+ remains inside cell
- more contraction
How do sympathetic mimetics increase contractility of heart (beta-1 agonist)
- phosphorylate Ca2+ channel
- increase VGCaC activity
- more Ca2+ enters, so greater contraction
Which enzyme is coupled to a beta-1 adrenergic receptor? GPCR
GaS; adenylate cyclase
How does activation of PKA lead to faster repolarisation (phase 3)
- increased K+ channel activity so more K+ ions can leave cell
- cell becomes more negative (repolarisation)
- shorter action potential, faster heart rate
What is amrinone?
- positive inotrope, increases strength of contraction
- brand name; inocor
- inhibits phosphodiesterase, PDE3
- therefore cAMP isn’t broken down, more PKA available to phosphorylate VGCaC
- more Ca2+ influx, more contraction
- only used in heart transplants
