2004 Fiscal Year Final Research Report Summary

general anesthetics modulation of GABAA receptor single-channnel currents

Research Project

Project/Area Number	15591662
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Anesthesiology/Resuscitation studies
Research Institution	Nippon Medical School
Principal Investigator	KITAMURA Akira Nippon Medical School, Department of Anesthesiology, assistant professor, 医学部, 講師 (30291719)
Project Period (FY)	2003 – 2004
Keywords	general anesthetics / mechanism / patch clamp / ion channel
Research Abstract	Halothane and propofol enhance the activity of the GABAA system, which 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.