IndraLab

"Knockout of HCN1 channels prevents the emergence of ketamine’s antidepressant and neuroplastic effects (141)."

"Thus, blockade of presynaptic NMDARs and HCN1 channels may limit ketamine efficacy.Optimizing subunit selectivity might improve NMDAR antagonist tolerability or efficacy, although the path forward is not clear."

"Ketamine is also a potent inhibitor of HCN1 ion channels and the associated ionic current I(h), with knockout of HCN1 channels reducing the hypnotic and dissociative actions of ketamine ."

"HCN1 mediated interactions of ketamine and propofol in a mean field model of the EEG."

"Therefore, the extant data support the hypothesis that NMDAR antagonism mediates the antidepressant effects of esketamine.Nevertheless, a recent preclinical study hypothesized that the hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) mediates the dissociative effects of ketamine (Vesuna et al., 2020)."

"To localize the brain region responsible for HCN1 mediated hypnotic actions of ketamine, we employed a conditional knockout strategy to delete HCN1 channels selectively in excitatory cells of the mouse forebrain."

"We suggest that ketamine inhibition of HCN1 shifts cortical neuron electroresponsive properties to contribute to ketamine induced hypnosis."

"Ketamine is also a potent inhibitor of HCN1 ion channels and the associated ionic current I(h), with knockout of HCN1 channels reducing the hypnotic and dissociative actions of ketamine ."

"In line with this, HCN1 channels were found to mediate the hypnotic actions of ketamine, 160 , 161 and the dopamine receptors affected the antidepressant effects and abuse potential of ketamine."

"Thus, the accumulated evidence available to this point is consistent with the idea that forebrain HCN1 channels indeed contribute to ketamine induced hypnosis."

"This new result suggests that forebrain HCN1 channels contribute to ketamine induced hypnosis, but does not rule out significant contributions by hindbrain HCN1 channels or by other channels affected by ketamine."

"Elucidating these mechanisms is crucial for refining anesthetic techniques and bolstering patient safety protocols.Postoperative pain, a prevalent issue following joint replacement surgery, can inflict both physical and psychological distress, potentially escalating the risk of delirium.38 Ketamine exerts its analgesic effects through antagonism of the NMDA receptor and inhibition of the hyperpolarisation-activated cyclic nucleotide-gated 1 (HCN1) channel.39 Evidence from a systematic review supports intraoperative ketamine infusion as an effective adjunct for postoperative pain management, potentially minimizing opioid-related side effects."