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

1. Guinea-pig ventricle was used in the RNase protection assays to determine which α-isoforms of the Na⁺-K⁺ pumps are present, and ventricular myocytes were used in whole cell patch clamp studies to investigate the actions of α- and β-adrenergic agonists on Na⁺-K⁺ pump current. 2. RNase protection assays showed that two isoforms of the α-subunit of the Na⁺-K⁺-ATPase are present in guinea-pig ventricle. The mRNA for the α₁-isoform comprises 82% of the total pump message, the rest being the α₂-isoform. 3. We have previously shown that β-adrenergic agonists affect Na⁺-K⁺ pump current (I(p) through a protein kinase A (PKA)-dependent pathway. We now show that these β-effects are targeted to the α₁-isoform of the Na⁺-K⁺ pumps. 4. We have also previously shown that α-adrenergic agonists increase I(p) through a protein kinase C (PKC)-dependent pathway. We now show that these α-isoform effects are targeted to the α₂-isoform of the Na⁺-K⁺ pumps. 5. These results suggest the effects of adrenergic activation on N⁺-K⁺ pump activity in the heart can be regionally specific, depending on which α-isoform of the Na⁺-K⁺ pump is expressed.