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HCN1-mediated interactions of ketamine and propofol in a mean field model of the EEG
BMC Neuroscience volume 14, Article number: O22 (2013)
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 .
We show here  that an established mean field model of electrocortical activity can predict the EEG changes induced by combining ketamine and propofol by taking into account merely the HCN1-mediated hyperpolarisations, but neglecting their supposed main mechanisms of action (NMDA and GABAA, respectively). See Figure 1.
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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Bojak, I., Day, H.C. & J Liley, D.T. HCN1-mediated interactions of ketamine and propofol in a mean field model of the EEG. BMC Neurosci 14, O22 (2013) doi:10.1186/1471-2202-14-S1-O22
- Potassium Channel
- Field Model
- Peak Frequency
- Anesthetic Agent