Cardiac Contraction Flashcards
How does the heart contract?
AP upstroke causes Na+ ions to depolarise T-tubules which activates VGCCs. Ca binds to the RyR on the SR -
release of Ca from the SR. Ca binds to troponin causing displacement of tropomyosin/troponin complex which exposes actin-myosin binding sites. Myosin thick filaments heads bind to these active sites and cross-bridges are formed. Myosin head flexes to move actin and Z line towards sarcomere centre: contraction occurs via ATPase activity which causes release of energy by converting ATP to ADP which causes the filaments to slide.
What are the 3 components of troponin and what do they do?
TnT - binds to tropomyosin
TnI - binds to actin filaments to hold tropomyosin in place - inhibitory subunit that prevents actin binding myosin
TnC - binds Ca and leads to displacement of tropomyosin and so exposes actin binding sites.
How does the heart relax?
An AP downstroke causes K+ ions to repolarise the T-tubules and thus close the VGCCs so no CICR occurs. Extrusion of Ca from the cell occurs by 30% by the Na-Ca exchanger (NCX). Ca uptake into the SR/ER via SR Ca ATPase (SERCA) – 70%. Uptake of Ca into mitochondria. Prevention of contraction mechanism – chambers relaxed and can fill with blood.
What is the name of drugs that correct acute or chronic HF?
How do they work?
Positive inotropes
They increase Ca by increasing VGCC activity and reducing Ca extrusion
What effect does NA have on the heart?
How does it do this?
It increases contractility
NA binds to beta 1 adrenoreceptors - adenylate cyclase converts ATP to cAMP and increases it levels – increases PKA – phosphorylation of VGCCs – increase activity – more Ca influx during plateau phase – more cytosolic Ca – more sliding filament mechanism and so more contractility.
What 4 effects do sympathetic nerves have on the heart?
Positive inotropic effect - increased contractility
Positive chronotropic effect - increased HR
Positive dromotropic effect - increased conduction through AVN
Lusitropic effect - increased rate of relaxation - SERCA
How does digoxin treat chronic HF?
Why is it not used a much anymore?
Digoxin inhibits Na/K ATPase so there is a build-up of Na and less extrusion of Ca by NCX. More Ca is taken up into stores and so there is a greater CICR.
It has bad side effects.
Name 2 other inotropic agents that are B1-adrenoreceptor stimulants.
Dobutamine
Dopamine
What hormone is given to patients to treat chronic HF who already are taking B-blockers?
What is its mechanism of action?
Glucagon
Acts at GPCR - stimulates Gs pathway - increases cAMP and PKA activity
What is Amrinone?
What is its mechanism of action and thus its outcome?
A type III phosphodiesterase inhibitor
It inhibits PDE. PDE usually converts cAMP into AMP so it cAMP and reduces PKA activity – reduces contractility. This drug inhibits this so there is a build up of cAMP - increased Ca influx.
