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- Title
Propofol block of I<sub>h</sub> contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons.
- Authors
Ying, Shui‐Wang; Abbas, Syed Y.; Harrison, Neil L.; Goldstein, Peter A.
- Abstract
Although the depressant effects of the general anesthetic propofol on thalamocortical relay neurons clearly involve γ-aminobutyric acid (GABA)A receptors, other mechanisms may be involved. The hyperpolarization-activated cation current ( Ih) regulates excitability and rhythmic firing in thalamocortical relay neurons in the ventrobasal (VB) complex of the thalamus. Here we investigated the effects of propofol on Ih-related function in vitro and in vivo. In whole-cell current-clamp recordings from VB neurons in mouse (P23–35) brain slices, propofol markedly reduced the voltage sag and low-threshold rebound excitation that are characteristic of the activation of Ih. In whole-cell voltage-clamp recordings, propofol suppressed the Ih conductance and slowed the kinetics of activation. The block of Ih by propofol was associated with decreased regularity and frequency of δ-oscillations in VB neurons. The principal source of the Ih current in these neurons is the hyperpolarization-activated cyclic nucleotide-gated (HCN) type 2 channel. In human embryonic kidney (HEK)293 cells expressing recombinant mouse HCN2 channels, propofol decreased Ih and slowed the rate of channel activation. We also investigated whether propofol might have persistent effects on thalamic excitability in the mouse. Three hours following an injection of propofol sufficient to produce loss-of-righting reflex in mice (P35), Ih was decreased, and this was accompanied by a corresponding decrease in HCN2 and HCN4 immunoreactivity in thalamocortical neurons in vivo. These results suggest that suppression of Ih may contribute to the inhibition of thalamocortical activity during propofol anesthesia. Longer-term effects represent a novel form of propofol-mediated regulation of Ih.
- Subjects
ANESTHETICS; CENTRAL nervous system depressants; AMINOBUTYRIC acid; NEURONS; NERVOUS system; NEUROSCIENCES
- Publication
European Journal of Neuroscience, 2006, Vol 23, Issue 2, p465
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2005.04587.x