Figure 1: A mechanistic explanation for the change of HCN surface expression is implicated in the cognitive deterioration under CCH and baclofen ameliorates cognitive impairment via restoring the changed HCN surface expression. Hypoperfusion significantly reduced the protein levels of 1a-4 and 1b-2, which lead to a reduction of HCN1 surface expression and increase in HCN2 surface expression. The ratio of HCN2/HCN1 surface expression was increased. And this should increase the propensity of the interaction of HCN2 isoform’s with HCN1, which might augment HCN1/HCN2 heteromerization and result in a higher contribution of heteromeric HCN channels to the macroscopic Ih accordingly. The altered Ih should contribute to pathological alteration of the hippocampal network and may be responsible for cognitive impairments caused by CCH. Baclofen can increase the expression and enhance the function of 1a-4 and 1b-2 in CCH rats that restores the decreased HCN1 surface expression and increased HCN2 surface expression, which ameliorates the cognitive impairment caused by CCH.