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 (Ip) in acutely isolated guinea pig ventricular myocytes.
Results:
Adenosine inhibited the high DHO-affinity pump current (Ih) 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 A2A receptor agonist CGS21680 and A3 receptor agonist Cl-IB-MECA did not affect Ih. Application of the selective A2A 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 Ih inhibition.
Conclusion:
The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of Ih via adenosine A1 receptors and the PKC-δ isoform.
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Acknowledgements
This project was supported by the Natural Science Foundation of Hebei Province (No 30200030).
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Zhang, Z., Guo, Hc., Zhang, Ln. et al. Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes. Acta Pharmacol Sin 30, 404–412 (2009). https://doi.org/10.1038/aps.2009.26
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DOI: https://doi.org/10.1038/aps.2009.26
