In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing. (October 2015)

• Record Type: Journal Article
• Authors: Wang, Jing; Mojumder, Deb Kumar; Yan, Jun; Xie, An; Standaert, Robert F.; Qian, Haohua; Pepperberg, David R.; Frishman, Laura J.
• Is Part Of: Experimental eye research. Volume 139(2015:Oct.)
• Page Start: 48
• Page End: 63
• Publication Date: 2015-10
• Subjects: Electroretinogram -- GABA -- GABA receptors -- Retina -- Retinal signaling; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2015.07.002
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: All three classes of receptors for the inhibitory neurotransmitter GABA (GABAR) are expressed in the retina. This study investigated roles of GABAR, especially GABAC R (GABA(A)-ρ), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABAC R versus pharmacological blockade using receptor antagonists. Brief full-field flash ERGs were recorded from anesthetized GABA C R −/− mice, and WT C57BL/6 (B6) mice, before and after intravitreal injection of GABAC R antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABAA R antagonist, SR95531; GABAB R antagonist, CGP, and agonist, baclofen. Intravitreal injections of TPMPA and SR95531 were also made in Brown Norway rats. The effect of 2-AEMP on GABA-induced current was tested directly in isolated rat rod bipolar cells, and 2-AEMP was found to preferentially block GABAC R in those cells. Maximum amplitudes of dark (DA) and light-adapted (LA) ERG b-waves were reduced in GABA C R −/− mice, compared to B6 mice, by 30–60%; a-waves were unaltered and oscillatory potential amplitudes were increased. In B6 mice, after injection of TPMPA (also in rats), 3-APMPA or 2-AEMP, ERGs became similar to ERGs of GABA C R −/− mice. Blockade of GABAA Rs and GABAB Rs, or agonism of GABAB Rs did not alter B6 DA b-wave amplitude. The negative scotopic threshold response (nSTR) was slightly less sensitive in GABA C R −/− than in B6 mice, and unaltered by 2-AEMP. However, amplitudes of nSTR and photopic negative response (PhNR), both of which originate from inner retina, were enhanced by TPMPA and 3-APMPA, each of which has GABAB agonist properties, and further increased by baclofen. The finding that genetic deletion of GABAC R, the GABAC R antagonist 2-AEMP, and other antagonists all reduced ERG b-wave amplitude, supports a role for GABAC R in determining the maximum response amplitude of bipolar cells contributing to the b-wave. GABAC R antagonists differed in their effects on nSTR and PhNR; antagonists with GABAB agonist properties enhanced light-driven responses whereas 2-AEMP did not. Highlights: GABAC receptor antagonist 2-AEMP blocked GABA-induced current in rod bipolar cells. Knockout or blockade of GABAC receptors reduced maximum ERG b-wave amplitude. Blockade of GABAA or B receptors, did not reduce b-wave amplitude. GABAB agonist properties of TPMPA and 3-APMPA did not alter b-wave amplitude. GABAB agonists increased amplitudes of ERG waves originating from inner retina.