B3W2 Trans Phys Flashcards
What does calcium bind to to change tropomyosin conformation?
Troponin C which changes Tni and TnT with it
Force per Cross Bridge
Force increases with the number of cross bridges
What removes calcium from myocyte from most to least removal?
Serca NCX PMCA and Mitochondria
Inotropy
Measure of contractility or force production
What effects inotropy?
Intracellular Ca
Affinity for Ca
Increased cross bridge duration
PkA effected components
Phosphorylates
L Type Calcium Channels increases Ca
RYR increases Ca
Phospholamban decreases Ca
TnI lowers affinity for Ca so Ca can reattach more
Lusitropy
Ability to relax
Inotropy Heart Failure
Calcium Leak through Ryr
Decreased Ca uptake
Removal of Ca from cell
less Ca available
Ionotropic Therapies
Digoxin
Calcium Sensitizer Levosimendan
cAMP mediated stimulation
PDE inhibitor
Digoxin
Improves Ventricular filling
Calcium Sensitizer Levosimendan
Binds to Troponin C when calcium is too high
Cardiac Myosin Binding Protein C
Regulates systolic ejection
When phosphorylated prolongs attachment of actin and myosin
Omecamtiv Mecarbil
Cardiac Myosin activator causes cross bridge to go into strongly bound state
Increased cross bridge binding = more force generation
OM in mouse model
Increases Ca sensitivity at low Ca
slows rate of cross bridge detachment
OM in humans
increase in contractility is submaximal
Prolongs cross bridge time so the heart is slower
improves systolic function but greatly hinder diastolic