11. Plasma membrane (part 2) Flashcards
Describe Na+,K + -ATPase crystal structure (4 domains)
T domain – transport
N domain – ATP/ADP binding
P domain – phosphorylation
A domain – phosphatase activity
What is the Postulated mechanism of the Na,K-ATPase?
1/ E1 conformation
-> High affinity for Na+ and ATP
2/ E2 conformation Low affinity for ATP
3/ 3 Na+ out and 2 K+ in: Electrogenic
4/ Consume 30-70% of the ATP production
What types of isoforms does Postulated mechanism of the Na,K-ATPase have?
α and β isoforms
What are inhibitors of Postulated mechanism of the Na,K-ATPase?
cardiac glycosides
Postulated mechanism of the Na,K-ATPase
-> What is the role of FXYD subunit?
FXYD subunit: modulator
In heart: phospholemman
3 examples of Cardiac glycosides
digitoxin, digoxin
ouabain
Composition of Digoxin
Cardiac glycosides (monosaccharide+steroid)
What is the role of Endogenous cardiac glycosides?
- regulation of renal sodium transport and arterial pressure
- Regulation of cell growth
- Differentiation
- Apoptosis
- Fibrosis
- Carbohydrate metabolism
What is Phospholamban?
a crucial regulator of cardiac contractility
The role of SERCA2
1/ removal of >70% of myoplasmic Ca2+
2/ determines both the rate of Ca2+ removal (and, consequently, the rate of cardiac muscle relaxation) and the size of the Ca2+ store (which affects cardiac contractility in the subsequent beat).
What happen if Phospholamban is phosphorylated?
Phosphorylated phospholamban
→SERCA2 activation
→ cardiac relaxation is increased and, on subsequent beats, contractility is increased
A ventricular cardiomyocyte
-> What happen when Ca2+ level elevates?
There will be a positive inotrop effect
A ventricular cardiomyocyte
-> What is the role of digitalis?
It increases vagal activity
A ventricular cardiomyocyte
-> Which therapy can be used for Digitalis toxicity?
Narrow therapeutic window
A ventricular cardiomyocyte
-> Symptoms of digitalis toxicity?
nausea, vomiting, diarrhea, bradicardia
