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

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Abstract
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 (Ip) 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 Ip 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 Na+‐K+ pump activity in the heart can be regionally specific, depending on which α‐isoform of the Na+‐K+ pump is expressed.