In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing
[1]
- Univ. of Houston, TX (United States). College of Optometry
- Univ. of Houston, TX (United States). College of Optometry; Texas Tech Univ., Lubbock, TX (United States). Dept. of Neurobiology
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Chengdu Kanghong Pharmaceutical Co., Sichuan (People's Republic of China)
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.; Brown Univ., Providence, RI (United States). Lifespan Cardiovascular Inst. and Warren Alpert School of Medicine
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division; Univ. of Tennessee, Knoxville, TN (United States). Dept. of Biochemistry and Molecular and Cellular Biology
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.; National Inst. of Health (NIH), Bethesda, MD (United States). National Eye Inst.
- Univ. of Illinois, Chicago, IL (United States). Lions of Illinois Eye Research Inst.
The retina expresses all three classes of receptors for the inhibitory neurotransmitter GABA (GABAR). Our study investigated roles of GABAR, especially GABA(C)R (GABA(A)-rho), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABA(C)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 GABA(C)R antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABA(A)R antagonist, SR95531; GABA(B)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 GABA(C)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 GABA(A)Rs and GABA(B)Rs, or agonism of GABA(B)Rs did not alter B6 DA b-wave amplitude. Furthermore, 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 GABA(B) agonist properties, and further increased by baclofen. The finding that genetic deletion of GABA(C)R, the GABA(C)R antagonist 2-AEMP, and other antagonists all reduced ERG b-wave amplitude, supports a role for CABA(C)R in determining the maximum response amplitude of bipolar cells contributing to the b-wave. GABA(C)R antagonists differed in their effects on nSTR and PhNR; antagonists with GABA(B) agonist properties enhanced light-driven responses whereas 2-AEMP did not.
- Research Organization:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- AC05-00OR22725
- OSTI ID:
- 1334449
- Journal Information:
- Experimental Eye Research, Vol. 139, Issue C; ISSN 0014-4835
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Contribution of GABAa, GABAc and glycine receptors to rat dark-adapted oscillatory potentials in the time and frequency domain
|
journal | September 2017 |
Similar Records
Neurochemical correlates of. gamma. -aminobutyrate (GABA) inhibition in cat visual cortex
Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex