Elucidating the role of HCN1 ion channels in sevoflurane-induced anterograde amnesia
Objective To investigate whether hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1) contributes to sevoflurane-induced anterograde amnesia. Method Wild-type and HCN1 knockout (HCN1-/-) C57BL/6J mice underwent contextual and cued fear conditioning under varying sevoflurane concentrations (0％,0.1％,0.2％,0.4％,0.6％,and 0.8％). Median effective concentration (EC50) values for sevoflurane inhibition of fear memory were calculated. The effect of sevoflurane (0.125 mmol/L) on HCN1 in human embryonic kidney 293 cells transfected with HCN1 (HEK293-HCN1) was recorded using whole-cell patch clamp technique. The changes in HCN1 before (control group) and after (sevoflurane group) sevoflurane treatment were compared. Result The EC50 for sevoflurane inhibition of contextual fear memory was significantly higher in HCN1-/-mice than in wild-type mice (0.26％ vs. 0.18％,P<0.001). The EC50 for cued fear memory inhibition was also higher in HCN1-/-mice (0.49％ vs. 0.47％,P<0.001),indicating HCN1 knockout attenuated sevoflurane-induced anterograde amnesia. 0.125 mmol/L sevoflurane inhibited HEK293-HCN1 cell current amplitude at ﹣90 mV to ﹣140 mV (all P<0.05) and shifted V1/2a from (﹣108±2.9) mV to (﹣100.1±3.0) mV (P<0.001),demonstrating an inhibitory effect on HCN1 currents. Conclusion Inhibition of HCN1 channel currents may contribute to the anterograde amnesic effects of sevoflurane.
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