Acta Pharmacologica Sinica (2009) 30: 404-412; doi: 10.1038/aps.2009.26; published online 23rd March 2009

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 A₁ receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific δ isoform antagonist rottlerin.  In addition, the inhibitory action of adenosine was mimicked by a selective A₁ receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114.  In contrast, the selective A _2A receptor agonist CGS21680 and A₃ receptor agonist Cl-IB-MECA did not affect I_h.  Application of the selective A _2A receptor antagonist SCH58261 and A₃ 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 A₁ receptors and the PKC-δ isoform.

Keywords: Na⁺-K⁺ pump; isoform; regulation; adenosine; patch-clamp techniques; protein kinase C