Fundamental & Clinical Pharmacology 2012-08-01

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

Linan Zhang, Fang Guo, Suwen Su, Huicai Guo, Chen Xiong, Jian Yin, Wenya Li, Yongli Wang

Index: Fundam. Clin. Pharmacol. 26(4) , 503-12, (2012)

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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(-3) M), 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.© 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.