Ketamine, propofol, and the EEG: A neural field analysis of HCN1-mediated interactions

Bojak, I. ORCID: https://orcid.org/0000-0003-1765-3502, Day, H. C. and Liley, D. T. J. (2013) Ketamine, propofol, and the EEG: A neural field analysis of HCN1-mediated interactions. Frontiers in Computational Neuroscience, 7. Article 22. ISSN 1662-5188 doi: 10.3389/fncom.2013.00022

Abstract/Summary

Ketamine and propofol are two well-known, powerful anesthetic agents, yet at first sight this appears to be their only commonality. Ketamine is a dissociative anesthetic agent, whose main mechanism of action is considered to be N-methyl-D-aspartate (NMDA) antagonism; whereas propofol is a general anesthetic agent, which is assumed to primarily potentiate currents gated by γ-aminobutyric acid type A (GABAA) receptors. However, several experimental observations suggest a closer relationship. First, the effect of ketamine on the electroencephalogram (EEG) is markedly changed in the presence of propofol: on its own ketamine increases θ (4–8 Hz) and decreases α (8–13 Hz) oscillations, whereas ketamine induces a significant shift to beta band frequencies (13–30 Hz) in the presence of propofol. Second, both ketamine and propofol cause inhibition of the inward pacemaker current Ih, by binding to the corresponding hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) subunit. The resulting effect is a hyperpolarization of the neuron’s resting membrane potential. Third, the ability of both ketamine and propofol to induce hypnosis is reduced in HCN1-knockout mice. Here we show that one can theoretically understand the observed spectral changes of the EEG based on HCN1-mediated hyperpolarizations alone, without involving the supposed main mechanisms of action of these drugs through NMDA and GABAA, respectively. On the basis of our successful EEG model we conclude that ketamine and propofol should be antagonistic to each other in their interaction at HCN1 subunits. Such a prediction is in accord with the results of clinical experiment in which it is found that ketamine and propofol interact in an infra-additive manner with respect to the endpoints of hypnosis and immobility.

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Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/32497
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary Research Centres (IDRCs) > Centre for Integrative Neuroscience and Neurodynamics (CINN) No Reading authors. Back catalogue items
Uncontrolled Keywords	ketamine, propofol, EEG, HCN1, neural field theory, drug interaction, anesthesia, infra-additivity
Additional Information	The full text of this article is freely available via PMC using the link supplied in Related URLs
Publisher	Frontiers
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