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Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons.
Eur J Neurosci. 2006 Jan; 23(2):465-80.EJ

Abstract

Although the depressant effects of the general anesthetic propofol on thalamocortical relay neurons clearly involve gamma-aminobutyric acid (GABA)(A) receptors, other mechanisms may be involved. The hyperpolarization-activated cation current (I(h)) 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 I(h)-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 I(h). In whole-cell voltage-clamp recordings, propofol suppressed the I(h) conductance and slowed the kinetics of activation. The block of I(h) by propofol was associated with decreased regularity and frequency of delta-oscillations in VB neurons. The principal source of the I(h) 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 I(h) 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), I(h) 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 I(h) may contribute to the inhibition of thalamocortical activity during propofol anesthesia. Longer-term effects represent a novel form of propofol-mediated regulation of I(h).

Authors+Show Affiliations

C.V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16420453

Citation

Ying, Shui-Wang, et al. "Propofol Block of I(h) Contributes to the Suppression of Neuronal Excitability and Rhythmic Burst Firing in Thalamocortical Neurons." The European Journal of Neuroscience, vol. 23, no. 2, 2006, pp. 465-80.
Ying SW, Abbas SY, Harrison NL, et al. Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons. Eur J Neurosci. 2006;23(2):465-80.
Ying, S. W., Abbas, S. Y., Harrison, N. L., & Goldstein, P. A. (2006). Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons. The European Journal of Neuroscience, 23(2), 465-80.
Ying SW, et al. Propofol Block of I(h) Contributes to the Suppression of Neuronal Excitability and Rhythmic Burst Firing in Thalamocortical Neurons. Eur J Neurosci. 2006;23(2):465-80. PubMed PMID: 16420453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Propofol block of I(h) contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons. AU - Ying,Shui-Wang, AU - Abbas,Syed Y, AU - Harrison,Neil L, AU - Goldstein,Peter A, PY - 2006/1/20/pubmed PY - 2006/4/28/medline PY - 2006/1/20/entrez SP - 465 EP - 80 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 23 IS - 2 N2 - Although the depressant effects of the general anesthetic propofol on thalamocortical relay neurons clearly involve gamma-aminobutyric acid (GABA)(A) receptors, other mechanisms may be involved. The hyperpolarization-activated cation current (I(h)) 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 I(h)-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 I(h). In whole-cell voltage-clamp recordings, propofol suppressed the I(h) conductance and slowed the kinetics of activation. The block of I(h) by propofol was associated with decreased regularity and frequency of delta-oscillations in VB neurons. The principal source of the I(h) 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 I(h) 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), I(h) 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 I(h) may contribute to the inhibition of thalamocortical activity during propofol anesthesia. Longer-term effects represent a novel form of propofol-mediated regulation of I(h). SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16420453/Propofol_block_of_I_h__contributes_to_the_suppression_of_neuronal_excitability_and_rhythmic_burst_firing_in_thalamocortical_neurons_ DB - PRIME DP - Unbound Medicine ER -