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-Aminobutyric AcidA Receptor Single-Channel Currents


*Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois; and
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan
Address correspondence and reprint requests to Toshio Narahashi, DVM, PhD, Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Address e-mail to narahashi{at}northwestern.edu
Halothane and propofol enhance the activity of the
-aminobutyric acid (GABA) system, which is one of the most important systems in the mechanism of anesthesia. To determine whether halothane and propofol enhance GABAergic responses by the same mechanism, we performed single-channel patch-clamp experiments with rat cortical neurons in primary culture. Each of the open-time and closed-time distributions of GABAA receptor single channels was expressed by a sum of fast and slow time constants. Neither halothane nor propofol changed the single-channel conductance. Halothane increased the probability of the channel being open via a prolongation of the slow phase of open time, whereas propofol increased the channel open probability via a shortening of the slow phase of closed time. Thus, although both halothane and propofol augmented the channel open probability, thereby causing an increase in charge transfer during inhibitory transmitter action, they acted by different mechanisms.
IMPLICATIONS: Although both halothane and propofol increase
-aminobutyric acid (GABA)-mediated synaptic inhibition, thereby causing anesthesia, the underlying mechanisms at the single GABA receptor channels have been shown to be different by using the patch-clamp technique.
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