Chloride Ions Preferentially Mask High‐Affinity GABA Binding Sites

Abstract

Chloride ions (Cl-) act to regulate the appearance of gamma-aminobutyric acid (GABA) binding sites in synaptic membranes from bovine retinas. Scatchard analysis indicates that the presence of Cl- results in a preferential decrease (85%) in the number of high-affinity binding sites, with no statistically significant change in the affinity (KD) of either the high- or low-affinity sites. The finding that the appearance of this binding site is altered by the presence of Cl- may indicate that Cl- acts, either directly or indirectly, to regulate the appearance, and hence function, of the high-affinity GABA receptor.

GABAA Receptor Populations Bind Agonists and Antagonists Differentially and with Opposite Affinities

“…The general validity of this view has been challenged by the recent report that thiocyanate could not enhance the [3H]GABA displacing potency of the new pyridazinyl-GABA antagonists (Heaulme et al, 1986). Chloride ions have also been shown to remove the high-affinity GABA binding sites (Madtes, 1984) and induce shifts in the displacing potencies of GABA agonists and antagonists similarly to thiocyanate (Olsen and Snowman, 1983). Therefore these effects of C1-and SCNhave been considered as common properties of Eccles anions penetrating through the attached chloride channel (Olsen and Snowman, 1983).…”

“…1984a), the displacing potency of SR 95 103 was significantly decreased ( Table 1). In contrast, the presence of C1ions, which reduces the number of high-affinity GABA sites (Madtes, 1984), shifted the displacing potency of SR 95103 in the opposite direction (Table 1).…”

“…Covalent modification of the synaptic membranes with p-diazobenzenesulfonic acid (DSA) or tetranitromethane selectively eliminated the low-affinity sites (Burch et al, 1983; Maksay and Ticku, 1984a). On the other hand, the presence of anions such as thiocyanate (Browner et al,198 1) or C1- (Madtes, 1984) removed the highaffinity population of sites. In the above systems the GABA-displacing potency of some GABA antagonists has been shifted opposite to that of GABA agonists, suggesting that GABA antagonists bind preferentially to the hydrophobic accessory sites around the low-affinity GABAA receptors (Maksay and Ticku, 1984b).…”

GABAA and GABAB sites in bovine adrenal medulla membranes

“…In addition, we did not find a Ca2' effect on our GABAA binding when the Ca2' concentrations were lower than 1 mM, while Majewska and Chuang (20) indicate that Ca2' is necessary for hgh-affinity GABAA sites in the brain. Thus, it is possible that these high-affinity GABAA sites could be absent from adrenal medulla or that they could be masked by C1-ions in the medium, as was reported for brain (21) (notice that we used Tris-HCl buffer).…”

Ion and Temperature Effects on the Binding of γ‐Aminobutyrate to Its Receptors and the High‐Affinity Transport System

“…Kardos et al (1 985) have studied the characteristics of GABA binding to cells grown in culture using a physiological incubation medium, and Yang and 01-sen ( 1987) recently have studied the effect of incubation temperature on the binding of muscimol to membranes prepared from mouse brain. Several studies on the effects of Na+ and C1-on GABAA receptor binding have been reported (Enna and Snyder, 1977;Hitzemann and Loh, 1978;Kurioka et al, 1981;Madtes, 1984), but these studies in general were performed at low temperatures, and predated the discovery of the GABAs receptor and the availability of compounds that selectively bind to each receptor type or the transport site.…”