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October 24, 2015
1:00:00 PM - 3:00:00 PM
Room Hall B2-Area B
Sevoflurane Reduces Intrinsic Neuronal Excitability of Thalamocortical Neurons in the Ventrobasal Complex
Elisabeth Koch, M.D., Stephan Kratzer, M.D., Gerhard Rammes, Ph.D., Eberhard F. Kochs, M.D., Manfred Blobner, M.D., Rainer Haseneder, M.D.
Klinikum rechts der Isar, TU Muenchen, Munich, Germany
Disclosures: E. Koch: None. S. Kratzer: None. G. Rammes: None. E.F. Kochs: None. M. Blobner: None. R. Haseneder: None.
Background and objectives: There is an ongoing discussion on the role of the thalamus in anesthetic-induced loss of consciousness (1). Since anesthetics at loss of consciousness cause a reduction of thalamic metabolism, the thalamus may serve as a consciousness switch (2). A reduction of thalamic excitability has been shown for intravenous as well as inhalative anesthetics. However, there is no detailed investigation of the effects of sevoflurane on excitability of thalamocortical (TC) relay neurons. In the present study, we investigated the effects of the commonly used volatile anesthetic sevoflurane on intrinsic neuronal excitability of TC neurons in the ventrobasal complex.

Methods: Acute brain slices with preserved thalamocortical connectivity (400 µm) were prepared from C57Bl/6N mice (3). Whole-cell patch-clamp recordings were performed in the current-clamp mode from TC neurons in the ventrobasal complex. TC neurons were identified according to their morphology and characteristic spiking patterns that depend on the membrane potential. After 10 minutes of stable control recordings, sevoflurane at a concentration of 3.2 vol.% (1.0 mouse MAC) was added to the perfusing carbogenated artificial cerebrospinal fluid. To determine the action potential threshold, currents of 500 ms duration were stepwise applied, beginning at -90 pA. A hyperpolarizing current step (-350 to -500 pA) was used to induce the HCN channel-mediated rectification in the membrane potential (voltage sag) and low-threshold Ca2+ spike rebound burst firing. Rebound delay was defined as the time course from the start of repolarization to the peak of the first action potential.

Results: Neuronal input resistance was decreased in the presence of sevoflurane from 186.9 ± 28.5 MΩ to 121.1 ± 23.1 MΩ (n=6, p<0.05). Sevoflurane shifted the action potential threshold from 126 ± 22.9 pA in control recordings to 228 ± 44.1 pA (n=5, p<0.05). The amplitude of the HCN channel-mediated voltage sag was significantly diminished by sevoflurane to 44.6 ± 11.6 % of control (n=6, p<0.05). Moreover, rebound delay was prolonged from 62.8 ± 8.1 ms to 112.8 ± 23.1 ms (n=6, p<0.05).

Discussion and conclusions: In the present study, we could demonstrate that sevoflurane impairs the HCN channel-mediated voltage sag and rebound burst. The shift of the action potential threshold to more depolarized membrane potentials also indicates a reduced neuronal excitability of TC neurons under sevoflurane. Both effects could result in reduced thalamocortical signal propagation and thus probably contribute to the hypnotic properties of sevoflurane.

References: 1. Mashour GA, Anesthesiology. 2015 Mar 6.; 2. Alkire MT et al., Science 2008 322:876-880; 3. Agmon A et al., Neuroscience 1991 41:365-379

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