Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart

Mol Cell. 1999 May;3(5):555-63. doi: 10.1016/s1097-2765(00)80349-4.

Abstract

It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ 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 Ca2+ signaling during cardiac contraction.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology
  • Enzyme Inhibitors / pharmacology
  • Glycosides / pharmacology
  • Heart Failure / enzymology
  • Heart Ventricles / cytology
  • Heart Ventricles / enzymology
  • Heterozygote
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / enzymology
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocardium / cytology
  • Myocardium / enzymology*
  • Ouabain / pharmacology
  • RNA, Messenger / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Stem Cells

Substances

  • Enzyme Inhibitors
  • Glycosides
  • Isoenzymes
  • RNA, Messenger
  • Ouabain
  • Sodium-Potassium-Exchanging ATPase
  • Calcium