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

Abstract

1. Guinea-pig ventricle was used in the RNase protection assays to determine which á-isoforms of the Na¤-K¤ pumps are present, and ventricular myocytes were used in whole cell patch clamp studies to investigate the actions of á-and â-adrenergic agonists on Na¤-K¤ pump current. 2. RNase protection assays showed that two isoforms of the á-subunit of the Na¤-K¤-ATPase are present in guinea-pig ventricle. The mRNA for the á1-isoform comprises 82% of the total pump message, the rest being the áµ-isoform. 3. We have previously shown that â-adrenergic agonists affect Na¤-K¤ pump current (Ip) through a protein kinase A (PKA)-dependent pathway. We now show that these â-effects are targeted to the á1-isoform of the Na¤-K¤ pumps. 4. We have also previously shown that á-adrenergic agonists increase Ip through a protein kinase C (PKC)-dependent pathway. We now show that these á-isoform effects are targeted to the áµ-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 á-isoform of the Na¤-K¤ pump is expressed.8785

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

“…Specifically, this inhibition is predominantly mediated by the novel PKC-δ isoform. Our results are consistent with those of Gao et al [4] , who demonstrated that I h was specifically regulated by PKC. However, in their study, I h was increased by α-adrenoceptor stimulation via the PKC pathway, which is not congruent with our result showing a PKC-δ-mediated decrease in I h .…”

“…Numerous studies over the years have highlighted the isoform-specific modulation of Na + -K + pumps by transmitters or kinases in many types of cells [4,25,26] . In this study, we found that the α 2 -isoform Na + -K + pumps are specifically inhibited by adenosine.…”

“…There are two possible explanations for the above results. First, the A 2A R is coupled to the cAMP-PKA pathway [28,29] , which is targeted to the α 1 -isoform of the Na + -K + pump [4] . Hence, A 2A R activation could not lead to any change in I h .…”

“…For instance, Alzamora et al [5] demonstrated that aldosterone has a non-genomic effect on the Na + -K + pump of vascular tissue, which is mediated by PKC activation. In patch-clamped guinea pig ventricular myocytes, Gao et al [4] showed that the high DHO-affinity pump current (I h ) is regulated by α-adrenergic agonists via a PKC-dependent pathway, whereas the low DHO-affinity pump current (I l ) is regulated by β-adrenergic agonists via a PKA-dependent pathway.…”

“…In guinea pig (Cavia sp.) ventricular myocytes, only the α 1 -and α 2 -isoforms, which correspond to the low-and highaffinity isoforms for cardiac glycosides, respectively, are expressed [3,4] .…”