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

Abstract

Aim: The present study investigated the effect of adenosine on Na-K pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes. Methods: The whole-cell, patch-clamp technique was used to record the Na-K pump current (I p) in acutely isolated guinea pig ventricular myocytes. Results: Adenosine inhibited the high DHO-affinity pump current (I h) in a concentration-dependent manner, which was blocked by the selective adenosine A 1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A 1 receptor agonist CCPA and a specific activator peptide of PKC-, PP114. In contrast, the selective A 2A receptor agonist CGS21680 and A 3 receptor agonist Cl-IB-MECA did not affect I h. Application of the selective A 2A receptor antagonist SCH58261 and A 3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Furthermore, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced I h inhibition. Conclusion: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of I h via adenosine A 1 receptors and the PKC- isoform. © 2009 CPS and SIMM.