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Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons.
J Neurophysiol. 2005 Apr; 93(4):1935-48.JN

Abstract

The GABAergic reticular thalamic nucleus (RTN) is a major source of inhibition for thalamocortical neurons in the ventrobasal complex (VB). Thalamic circuits are thought to be an important anatomic target for general anesthetics. We investigated presynaptic actions of the intravenous anesthetic propofol in RTN neurons, using RTN-retained and RTN-removed brain slices. In RTN-retained slices, focal and bath application of propofol increased intrinsic excitability, temporal summation, and spike firing rate in RTN neurons. Propofol-induced activation was associated with suppression of medium afterhyperpolarization potentials. This activation was mimicked and completely occluded by the small conductance calcium-activated potassium (SK) channel blocker apamin, indicating that propofol could enhance RTN excitability by blocking SK channels. Propofol increased GABAergic transmission at RTN-VB synapses, consistent with excitation of presynaptic RTN neurons. Stimulation of RTN resulted in synaptic inhibition in postsynaptic neurons in VB, and this inhibition was potentiated by propofol in a concentration-dependent manner. Removal of RTN resulted in a dramatic reduction of both spontaneous postsynaptic inhibitory current frequency and propofol-mediated inhibition of VB neurons. Thus the existence and activation of RTN input were essential for propofol to elicit thalamocortical suppression; such suppression resulted from shunting through the postsynaptic GABA(A) receptor-mediated chloride conductance. The results indicate that propofol enhancement of RTN-mediated inhibitory input via blockade of SK channels may play a critical role in "gating" spike firing in thalamocortical relay neurons.

Authors+Show Affiliations

C.V. Starr Laboratory for Molecular Neuropharmacology, Deptartment of Anesthesiology A-1050, Weill Medical College, Cornell University, 1300 York Ave., New York, NY 10021, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15563549

Citation

Ying, Shui-Wang, and Peter A. Goldstein. "Propofol-block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons." Journal of Neurophysiology, vol. 93, no. 4, 2005, pp. 1935-48.
Ying SW, Goldstein PA. Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons. J Neurophysiol. 2005;93(4):1935-48.
Ying, S. W., & Goldstein, P. A. (2005). Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons. Journal of Neurophysiology, 93(4), 1935-48.
Ying SW, Goldstein PA. Propofol-block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons. J Neurophysiol. 2005;93(4):1935-48. PubMed PMID: 15563549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons. AU - Ying,Shui-Wang, AU - Goldstein,Peter A, Y1 - 2004/11/24/ PY - 2004/11/26/pubmed PY - 2005/4/29/medline PY - 2004/11/26/entrez SP - 1935 EP - 48 JF - Journal of neurophysiology JO - J Neurophysiol VL - 93 IS - 4 N2 - The GABAergic reticular thalamic nucleus (RTN) is a major source of inhibition for thalamocortical neurons in the ventrobasal complex (VB). Thalamic circuits are thought to be an important anatomic target for general anesthetics. We investigated presynaptic actions of the intravenous anesthetic propofol in RTN neurons, using RTN-retained and RTN-removed brain slices. In RTN-retained slices, focal and bath application of propofol increased intrinsic excitability, temporal summation, and spike firing rate in RTN neurons. Propofol-induced activation was associated with suppression of medium afterhyperpolarization potentials. This activation was mimicked and completely occluded by the small conductance calcium-activated potassium (SK) channel blocker apamin, indicating that propofol could enhance RTN excitability by blocking SK channels. Propofol increased GABAergic transmission at RTN-VB synapses, consistent with excitation of presynaptic RTN neurons. Stimulation of RTN resulted in synaptic inhibition in postsynaptic neurons in VB, and this inhibition was potentiated by propofol in a concentration-dependent manner. Removal of RTN resulted in a dramatic reduction of both spontaneous postsynaptic inhibitory current frequency and propofol-mediated inhibition of VB neurons. Thus the existence and activation of RTN input were essential for propofol to elicit thalamocortical suppression; such suppression resulted from shunting through the postsynaptic GABA(A) receptor-mediated chloride conductance. The results indicate that propofol enhancement of RTN-mediated inhibitory input via blockade of SK channels may play a critical role in "gating" spike firing in thalamocortical relay neurons. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/15563549/Propofol_block_of_SK_channels_in_reticular_thalamic_neurons_enhances_GABAergic_inhibition_in_relay_neurons_ DB - PRIME DP - Unbound Medicine ER -