Pharmacology of GABA receptor CI− channels in rat retinal bipolar cells

Abstract

gamma-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian nervous system, is known to operate bicuculline-sensitive Cl- channels through GABAA receptors and bicuculline-insensitive cation channels through GABAB receptors. Recent observations indicate that the retina may contain GABA receptors with unusual pharmacological properties. Here we report that GABA gates bicuculline-insensitive Cl- channels in rod bipolar cells of the rat retina, which were not modulated by flunitrazepam, pentobarbital and alphaxalone and were only slightly blocked by picrotoxinin. Moreover, the GABAB receptor agonist baclofen, and the antagonist 2-hydroxysaclofen had no effect. The underlying single-channel conductance was 7 pS and the open time 150 ms. These values are clearly different from those obtained for GABAA receptor channels recorded in other neurons of the same preparation, and in other parts of the brain. The bicuculline- and baclofen-insensitive GABA receptors were activated selectively by the GABA analogue cis-4-aminocrotonic acid (CACA). Hence they may be similar to those receptors termed GABAC receptors.

Electrophysiological evidence of GABAA and GABAC receptors on zebrafish retinal bipolar cells

“…Invariably bipolar cells express a combination of GABA receptors, with the GABA A and/or GABA C types predominating. Our results showing GABA responses with the pharmacological properties of A-and C-type receptors on the processes of zebrafish bipolar cells are consistent with these previous immunocytochemical (Greferath et al, 1993;Yazulla & Studholme, 2001;Zhang et al, 2003;Klooster et al, 2004) and physiological (i.e., Feigenspan et al, 1993;Qian & Dowling, 1993Qian et al, 1997;Du & Yang, 2000;Qian et al, 2001) findings. GABA responses on isolated zebrafish bipolar cell dendrites were largely insensitive to bicuculline, but very sensitive to picrotoxin, suggesting these processes express GABA C -type receptors.…”

“…Though picrotoxin was an effective antagonist of GABA responses in isolated cells, a GABA response component sometimes remained (see Figure 6C), indicating an insensitive component could also be present on the dendrites. Though picrotoxin-insensitive GABA C receptors have been identified in rat bipolar cells (Feigenspan et al, 1993;Feigenspan & Bormann, 1994), this finding is in contrast to reports from other teleost retinas (Tachibana & Kaneko, 1987;Qian & Dowling, 1993;Matthews et al, 1994;Qian & Dowling, 1994Han et al, 1997).…”

“…Typically both picrotoxin-sensitive and insensitive subtypes are found on the same cell. This pharmacological pattern, while somewhat distinctive to zebrafish, displays characteristics similar to those found in other fish (Tachibana & Kaneko, 1987;Qian & Dowling, 1993;Matthews et al, 1994;Qian & Dowling, 1994Han et al, 1997), though picrotoxin-insensitivity has been identified only in rat (Feigenspan et al, 1993;Feigenspan & Bormann, 1994). TPMPA-insensitive GABA C receptors have not been previously reported, though a small GABA-evoked current remained in rabbit OFF-bipolar cells following co-application of bicuculline and TPMPA (Zhou & Dacheux, 2005).…”

The expression of GABAAreceptors during the development of the rabbit retina

“…These different subunits have different locations and properties in the retina (Enz et al 1995;Brandstätter et al 1995;Greferath et al 1995;Sassoë-Pognetto et al 1995;Ehinger & Zucker, 1996;Zucker & Ehinger, 1998). GABA A receptors are ligand gated ion channels in which the GABA binding site is directly linked to a chloride channel, but it is not yet well understood what these differences mean from a functional point of view (Feigenspan et al 1993). However, good monoclonal antibodies for some of the most common GABA A receptors are available (the alpha 1 and beta 2/3 subunits; monoclonal antibodies bd24 and bd17) and they are likely to be useful also for studies on the developing retina.…”

Cholecystokinin-like immunoreactive amacrine cells in the rat retina

“…We show that some gCCK-IR cells contact substance P-IR cells and that some gCCK-IR cells also contain substance P. The third goal was to investigate physiological actions of CCK in the retina. GABA A and GABA C receptors have been described on the rod bipolar cells of the rat (Feigenspan et al, 1993) and mouse retina (Vaquero & de la Villa, 1999). We show that CCK-8 partially inhibits GABA C -mediated currents, but not GABA A -mediated currents in dissociated rod bipolar cells.…”