- Oral presentation
- Open Access
HCN1-mediated interactions of ketamine and propofol in a mean field model of the EEG
© Bojak et al; licensee BioMed Central Ltd. 2013
- Published: 8 July 2013
- Potassium Channel
- Field Model
- Peak Frequency
- Anesthetic Agent
Ketamine and propofol, two popular anesthetic agents, are generally believed to operate via disparate primary mechanisms: ketamine through NMDA antagonism and propofol through the potentiation of GABAA-gated receptor currents. However, surprisingly the effect of ketamine on the EEG is markedly altered in the presence of propofol. Specifically, while ketamine alone results in a downshift of the peak frequency of the alpha rhythm, and propofol keeps it roughly constant - when administered together, they increase the alpha peak frequency .
Recently it has been found that both ketamine and propofol inhibit the hyperpolarization-activated cyclic nucleotide-gated potassium channel form 1 (HCN1) subunits, which induces neuronal membrane hyperpolarization . Furthermore, HCN1 knockout mice are significantly less susceptible to hypnosis with these agents; but equally affected by HCN1-neutral etomidate .
Our results suggest that ketamine and propofol are infra-additive in their HCN1-mediated actions. This is consistent with independent experimental evidence. We show here that the HCN1-mediated actions of ketamine and propofol, hitherto neglected by models of anaesthetic action, can not only explain a range of counterintuitive induced EEG changes but also predicts the infra-additivity of these drugs.
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