TY - JOUR

T1 - Potentiating action of propofol at GABAA receptors of retinal bipolar cells

AU - Yue, Lan

AU - Xie, An

AU - Bruzik, Karol S

AU - Frølund, Bente Flensborg

AU - Qian, Haohua

AU - Pepperberg, David R

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol delivered by brief application in combination with GABA or other pharmacologic agents or as a component of the superfusing medium. Results. When applied with GABA at subsaturating concentrations and with TPMPA (a known GABA(C) antagonist), propofol markedly increased the peak amplitude and altered the kinetics of the response. Propofol increased the response elicited by THIP (a GABA(A)-selective agonist), and the response was reduced by bicuculline (a GABA(A) antagonist). The response to 5-methyl I4AA, a GABA(C)-selective agonist, was not enhanced by propofol. Serial brief applications of (GABA + TPMPA + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced by (GABA + TPMPA + propofol) applications. Conclusions. Propofol exerts a marked and selective potentiation on GABA(A) receptors of retinal bipolar cells. The data encourage the use of propofol in future studies of bipolar cell function.

AB - Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol delivered by brief application in combination with GABA or other pharmacologic agents or as a component of the superfusing medium. Results. When applied with GABA at subsaturating concentrations and with TPMPA (a known GABA(C) antagonist), propofol markedly increased the peak amplitude and altered the kinetics of the response. Propofol increased the response elicited by THIP (a GABA(A)-selective agonist), and the response was reduced by bicuculline (a GABA(A) antagonist). The response to 5-methyl I4AA, a GABA(C)-selective agonist, was not enhanced by propofol. Serial brief applications of (GABA + TPMPA + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced by (GABA + TPMPA + propofol) applications. Conclusions. Propofol exerts a marked and selective potentiation on GABA(A) receptors of retinal bipolar cells. The data encourage the use of propofol in future studies of bipolar cell function.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1167/iovs.10-5991

DO - 10.1167/iovs.10-5991

M3 - Journal article

C2 - 21071744

VL - 52

SP - 2497

EP - 2509

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 5

ER -