[PDF][PDF] Identification of a specific role for the Na, K-ATPase α2 isoform as a regulator of calcium in the heart

PF James, IL Grupp, G Grupp, AL Woo, GR Askew… - Molecular cell, 1999 - cell.com
PF James, IL Grupp, G Grupp, AL Woo, GR Askew, ML Croyle, RA Walsh, JB Lingrel
Molecular cell, 1999cell.com
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 α1 or α2 isoforms clearly demonstrates different functional
roles for these isoforms in vivo. Heterozygous α2 hearts are hypercontractile as a result of …
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 α1 or α2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous α2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous α1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the α2 isoform with ouabain increases the contractility of heterozygous α1 hearts. These results definitively illustrate a specific role for the α2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.
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