Halothane and propofol modulation of gamma-aminobutyric acidA receptor single-channel currents.
Halothane and propofol enhance the activity of the gamma-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 GABA(A) 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.
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611, USA.
Akira
A
Kitamura
Ryoichi
R
Sato
William
W
Marszalec
Jay Z
JZ
Yeh
Ryo
R
Ogawa
Toshio
T
Narahashi
D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007473:Ion Channels; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D006221:Halothane; D015742:Propofol