Zusammenfassung
It is well accepted that inhibition of the Na,K-ATPase in the heart,
through effects on the Na/Ca exchanger, raises the intracellular
Ca$^2+$ concentration and strengthens cardiac contraction. However,
the contribution that individual isoforms make to this calcium regulatory
role is unknown. Assessing the phenotypes of mouse hearts with genetically
reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly
demonstrates different functional roles for these isoforms in vivo.
Heterozygous alpha 2 hearts are hypercontractile as a result of increased
calcium transients during the contractile cycle. In contrast, heterozygous
alpha 1 hearts are hypocontractile. The different functional roles
of these two isoforms are further demonstrated since inhibition of
the alpha 2 isoform with ouabain increases the contractility of heterozygous
alpha 1 hearts. These results definitively illustrate a specific
role for the alpha 2 Na,K-ATPase isoform in Ca$^2+$ signaling
during cardiac contraction.
- /&/
- animals;
- antagonists
- atpase,
- calcium
- calcium,
- cells
- contraction,
- cytology/enzymology;
- drug
- effects/physiology;
- enzyme
- enzymology;
- failure,
- fibers,
- glycosides,
- heart
- heterozygote;
- inhibitors,
- inhibitors/genetics/metabolism;
- isoenzymes,
- messenger,
- metabolism;
- mice,
- mice;
- muscle
- myocardial
- myocardium,
- ouabain,
- pharmacology;
- physiology;
- rna,
- signaling,
- sodium-potassium-exchanging
- stem
- transgenic;
- ventricles,
Nutzer