Cardiac contraction Flashcards
What is the duration of an action potential?
200-500ms
what is the amount of diastolic Ca2+?
100nM
What is the amount of systolic Ca2+?
10 μM
What is cell shortening like?
sub-maximal (not all or nothing)
When does cell shortening happen?
During depolarization ‘plateau’ phase of action potential when ICa is generated
When does cell relaxation happen?
During repolarisation of action potential
When Ca2+ signal is reduced
How does electrical excitability contract cardiac myocytes?
- contraction is determined by an increase Ca2+
- Greater increases Ca2+ = increased force of contraction
- Intracellular Ca2+ levels increase from 0.1 μM to about 10 μM
What are T tubules?
→ Extensions of the cell membrane (sarcolemma) that penetrate into the center of cardiac muscle cells
What is the sarcoplasmic reticulum?
→ Membrane bound structure within muscle cells similar to the endoplasmic reticulum in other cells and stores Ca 2+
What is a ryanodine receptor?
→ Intracellular Ca2+ channel
What is the process of cardiac contraction?
→ Action potential depolarizes T tubules and activates VGCC causing a Ca2+ influx
→ Ca2+ binds to RyR located on the SR - close association with T tubules
→ Release of Ca2+ from the SR - CICR
→Ca2+ binds to troponin and there is displacement of tropomyosin / troponin complex which exposes the active sites on the actin
→Myosin thick filament heads bind to the active sites
→Myosin head ATPase activity releases energy (ATP to ADP) and the filaments slide
What are the myosin-actin binding sites blocked by at rest?
→ Troponin-tropomyosin complex
How does a rise in calcium cause the actin-myosin cross bridge to be formed?
→Ca2+ displaces troponin-tropomyosin so the actin-myosin binding sites are exposed and an actin-myosin cross bridge is formed
What does a rise in Ca2+ cause?
→ More sites exposed
→ More cross-bridges
→ Greater contractility
What is troponin composed of?
→ 3 regulatory sub units
What is TnT?
→ Troponin T which binds to tropomyosin
What is TnI?
→ Troponin I which binds to actin filaments
What is TnC?
→ Troponin C binds Ca2+
What does binding of Ca2+ to TnC lead to?
→ conformational changes of tropomyosin and the exposure of actin binding sites
What are TnI and TnT markers for?
→ Plasma markers for cardiac cell death
→ following MI
How does relaxation occur?
→ Action potential repolarization (K+ ions) repolarize T tubules
→ VGCC close and there is a decrease of Ca2+ influx
→ There is no Ca2+ influx so no CICR
→ Extrusion of Ca2+ from the cell (30%) by the Na+/Ca2+ exchanger
→ Ca2+ uptake into the SR via SR Ca2+ ATPase (SERCA 70%) Ca2+ in SR for next contraction
→ Uptake of Ca2+ in mitochondria
→ Reduction in Ca2+ myosin head ATPase activity releases energy (ATP to ADP)
→ Prevention of contraction mechanism
What are drugs used for in relation to contractility?
→ used to increase contractility of the heart
→ correct acute chronic heart failure
What do sympathetic mimetic drugs do?
→ Increase VGCC activity
What do cardiac glycosides do and what are they used for ?
→ Reduce Ca2+ extrusion
→ used for chronic heart failure
