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A. Xie, L. Yue, F. Feng, D. R. Pepperberg, H. Qian; Propofol Potentiates GABA-Elicited Responses of Bipolar and Ganglion Cells in Rat Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1865.
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© ARVO (1962-2015); The Authors (2016-present)
Propofol (2,6-diisopropyl phenol), a known anesthetic agent, can potentiate GABAA receptor activity. We previously reported that propofol substantially enhances GABAA receptor-mediated currents in acutely isolated retinal bipolar cells (Yue et al., 2009 ARVO). In the present study, we examined propofol modulation of GABAA receptor activity in bipolar cells and ganglion cells (GCs) of rat retina.
Whole-cell patch-clamp techniques were used to record membrane currents and action potentials from bipolar cells and GCs in retinal slices obtained from adult rat. Propofol and TPMPA at defined concentrations were applied as a supplement to medium superfusing the slice; other pharmacological agents were delivered from a puff pipette. The extent of GABAA receptor activation was controlled by varying the puff duration. As needed, 4 mM Co2+ was used to block synaptic transmission.
In bipolar cells, propofol enhanced the current induced by puffed THIP (500 µM). At a fixed duration of the THIP puff, propofol's potentiation of the bipolar cell response increased with propofol concentration over the range of 100-1600 µM propofol, with an EC50 of 440 µM (100-ms puff) and 740 µM (5-ms puff). At a fixed high concentration of propofol (1.6 mM), potentiation decreased with increasing THIP puff duration, from 5.3-fold (5-ms puff) to 2.7-fold (100-ms puff). The bipolar cell response to 1 mM GABA in the presence of 4 mM Co2+ was mediated primarily by GABAA receptors, as this response was not significantly altered by 200 µM TPMPA. (Here, Co2+ likely blocked GABAC receptors, as 4 mM Co2+ inhibited GABAC activity in acutely isolated bipolar cells.) However, in the presence of 200 µM propofol, TPMPA enhanced the bipolar cell response induced by a short puff of GABA. TPMPA enhancement was also observed for the bipolar cell response to muscimol recorded in retinal slices, but not for GABAA receptors expressed in Xenopus oocytes or in acutely isolated rat bipolar cells. In GCs of retinal slices, propofol enhanced GABAA receptor activity produced by either THIP or GABA, and enhanced the peak amplitude and prolonged the decay time of spontaneous IPSCs. In ON-type GCs, propofol reduced the frequency of action potentials elicited by light.
Propofol potentiates GABAA receptor activity in bipolar cells and GCs in rat retinal slices. Propofol's potentiation of GABAA activity may underlie the observed reduction in the GC light response.
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