HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice
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Jie Gao1,2, Zhiqiang Hu1,2, Liwei Shi1,2, Na Li1,2, Yeling Ouyang1,2, Shaofang Shu1,2, Shanglong Yao1,2 and Xiangdong Chen1,2
1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
2Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Xiangdong Chen, email: [email protected]
Keywords: HCN channels; intravenous anesthetics; development; sensitivity
Received: September 01, 2017 Accepted: January 13, 2018 Published: February 05, 2018
It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics. Here we showed the EC50 for propofol- and ketamine-induced loss-of-righting reflex (LORR) was significantly lower for P35 than for P14 mice. Cerebrospinal fluid concentrations of propofol and ketamine were significantly higher in P14 mice than in P35 mice, with similar propofol- and ketamine-induced anesthesia at the LORR EC50. Western blotting indicated that the expression of HCN channels in neocortex changed significantly from P14 to P35 mice. In addition, the amplitude of HCN currents in the neocortical layer 5 pyramidal neurons and the inhibition of propofol and ketamine on HCN currents dramatically increased with development. Logistic regression analysis indicated that the changes of HCN channels were correlated with the age-related differences of propofol- and ketamine-induced anesthesia. These data reveal that the change of HCN channels expression with postnatal development may contribute to sensitivity to the hypnotic actions of propofol and ketamine in mice.
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