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


CONCLUSIONS
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.
Zhang
Zhe
Z
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Guo
Hui-cai
HC
Zhang
Li-nan
LN
Wang
Yong-li
YL
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms / Q000502:physiology; D051745:Protein Kinase C-delta / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000502:physiology; D043705:Receptor, Adenosine A2A / Q000502:physiology; D043684:Receptor, Adenosine A3 / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D020033:Protein Isoforms; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D017868:Cyclic AMP-Dependent Protein Kinases; D051745:Protein Kinase C-delta; D000254:Sodium-Potassium-Exchanging ATPase; D000241:Adenosine