Department of Anesthesiology

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Propofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons.

TitlePropofol-block of SK channels in reticular thalamic neurons enhances GABAergic inhibition in relay neurons.
Publication TypeJournal Article
Year of Publication2005
AuthorsYing S-W, Goldstein PA
JournalJ Neurophysiol
Volume93
Issue4
Pagination1935-48
Date Published2005 Apr
ISSN0022-3077
KeywordsAction Potentials, Animals, GABA-A Receptor Antagonists, Mice, Mice, Inbred C57BL, Neural Inhibition, Neurons, Potassium Channel Blockers, Potassium Channels, Calcium-Activated, Propofol, Receptors, GABA-A, Small-Conductance Calcium-Activated Potassium Channels, Thalamus
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.

DOI10.1152/jn.01058.2004
Alternate JournalJ. Neurophysiol.
PubMed ID15563549
Grant ListGM-66840 / GM / NIGMS NIH HHS / United States
R01 GM066840-01A1 / GM / NIGMS NIH HHS / United States