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We recently found astrocytes in primary culture expressed hyperpolarization-activated cyclic nucleotide-gated (HCN) genes (HCN2 and HCN4) and the hyperpolarization-activated cation current (Ih).The expressions of HCN genes and Ih currents were different between astrocytes and neurons.Here we demonstrated that both increase and decrease in [K+]. would down-regulate the gene expression levels.Changes of osmolarity and sodium content in the medium did not affect HCN2 gene expression.Increase of [K+]. can significantly up-regulate Ih current.Glutamate treatment alone did not affect the HCN2 gene expression and Ⅰh current in astrocyte.Co-treatments of glutamate and K+ could modulate the effect of K+ to the HCN2 gene expression and the glutamate effect was mediated by AMPA and NMDA receptors.Our findings indicate that the astrocytic HCN channel could respond to K+ and glutamate,2 major factors in neuronal excitation.Therefore,HCN might play an important role in controlling the resting membrane potential of astrocytes,thus contributing to the maintenance of electrophysiological homeostasis of the brain.