Volume 26, Issue 4 pp. 503-512
ORIGINAL ARTICLE

Na+/K+-ATPase inhibition upregulates NMDA-evoked currents in rat hippocampal CA1 pyramidal neurons

Linan Zhang

Linan Zhang

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

Pharmacy Department, Hebei University of Science and Technology, 70 Yuhua East Road, Shijiazhuang, Hebei 050018, China

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Fang Guo

Fang Guo

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Suwen Su

Suwen Su

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Huicai Guo

Huicai Guo

Department of Toxicology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Chen Xiong

Chen Xiong

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Jian Yin

Jian Yin

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Wenya Li

Wenya Li

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

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Yongli Wang

Corresponding Author

Yongli Wang

Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China

Correspondence and reprints: [email protected]; [email protected]Search for more papers by this author
First published: 26 April 2011
Citations: 12

Abstract

Na+/K+-ATPase and N-methyl-d-aspartate (NMDA) receptor in hippocampus play very important roles in the regulation of learning and memory. Here, we showed that dihydroouabain (DHO, 10−5–10−3m), a Na+/K+-ATPase inhibitor, significantly potentiated NMDA current in rat hippocampal CA1 pyramidal neurons, which was blocked by PP2 (the selective Src tyrosine kinase inhibitor) and PD-98059 [the selective inhibitor of the mitogen-activated protein kinases (MAPK) cascade]. These findings reported here uncover that Src mediates the cross-talk between Na+/K+-ATPase and NMDA receptor to transduce the signals from Na+/K+-ATPase to the MAPK cascade and provide new insights into therapeutic target for deeper understanding of the nature of cognitive disorder.

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