Isoform-specific regulation of the sodium pump by alpha- and beta-adrenergic agonists in the guinea-pig ventricle

J Physiol. 1999 Apr 15;516 ( Pt 2)(Pt 2):377-83. doi: 10.1111/j.1469-7793.1999.0377v.x.

Abstract

1. Guinea-pig ventricle was used in the RNase protection assays to determine which alpha-isoforms of the Na+-K+ pumps are present, and ventricular myocytes were used in whole cell patch clamp studies to investigate the actions of alpha- and beta-adrenergic agonists on Na+-K+ pump current. 2. RNase protection assays showed that two isoforms of the alpha-subunit of the Na+-K+-ATPase are present in guinea-pig ventricle. The mRNA for the alpha1-isoform comprises 82 % of the total pump message, the rest being the alpha2-isoform. 3. We have previously shown that beta-adrenergic agonists affect Na+-K+ pump current (Ip) through a protein kinase A (PKA)-dependent pathway. We now show that these beta-effects are targeted to the alpha1-isoform of the Na+-K+ pumps. 4. We have also previously shown that alpha-adrenergic agonists increase Ip through a protein kinase C (PKC)-dependent pathway. We now show that these alpha-isoform effects are targeted to the alpha2-isoform of the Na+-K+ pumps. 5. These results suggest the effects of adrenergic activation on Na+-K+ pump activity in the heart can be regionally specific, depending on which alpha-isoform of the Na+-K+ pump is expressed.

Publication types

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

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Guinea Pigs
  • Heart / drug effects*
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Heart Ventricles / enzymology
  • In Vitro Techniques
  • Isoenzymes / antagonists & inhibitors
  • Male
  • Molecular Sequence Data
  • Myocardium / cytology
  • Myocardium / enzymology
  • Patch-Clamp Techniques
  • Protein Kinase C / metabolism
  • RNA Probes
  • Ribonucleases / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Isoenzymes
  • RNA Probes
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Ribonucleases
  • Sodium-Potassium-Exchanging ATPase