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

作　　者：Zhe ZHANG Hui-cai GUO Li-nan ZHANG Yong-li WANG 

机构地区：[1]Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China

出　　处：《Acta Pharmacologica Sinica》2009年第4期404-412,共9页中国药理学报（英文版）

基　　金：This project was supported by the Natural Science Foundation of Hebei Province （No 30200030）.

摘　　要：Aim The present study investigated the effect of adenosine on Na^＋-K^＋ pumps in acutely isolated guinea pig （Cavia sp.） ven- tricular 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 6 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-5, PPl14. In contrast, the selective A2A receptor agonist CGS21680 and A3 receptor agonist CMB-MECA did not affect Ih. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRSl191 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-6 isoform.Aim The present study investigated the effect of adenosine on Na^＋-K^＋ pumps in acutely isolated guinea pig （Cavia sp.） ven- tricular 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 6 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-5, PPl14. In contrast, the selective A2A receptor agonist CGS21680 and A3 receptor agonist CMB-MECA did not affect Ih. Application of the selective A2A receptor antagonist SCH58261 and A3 receptor antagonist MRSl191 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-6 isoform.

关 键 词：Na^＋-K^＋ pump ISOFORM REGULATION ADENOSINE patch-clamp techniques protein kinase C 

分 类 号：R245.97[医药卫生—针灸推拿学] R331.38[医药卫生—中医临床基础]