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

The present study investigated the effect of adenosine on Na(+)-K(+) pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes.

The whole-cell, patch-clamp technique was used to record the Na(+)-K(+) pump current (I(p)) in acutely isolated guinea pig ventricular myocytes.

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 delta 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-delta, 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.

The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of I(h) via adenosine A(1) receptors and the PKC-delta isoform.