Modulation of GABAC response by Ca2+ and other divalent cations in horizontal cells of the catfish retina.
GABAC responses were recorded in cultured cone-driven horizontal cells from the catfish retina using the patch clamp technique. At a holding potential of -49 mV, a bicuculline-resistant inward current (IGABA) was observed when 10 microM GABA was applied. The amplitude of IGABA increased as the extracellular Ca2+ ([Ca2+]o) was increased. Concentration-response curves of IGABA at 2.5 and 10 mM -Ca2+-o had similar EC50 (3.0 and 3.1 microM) and Hill coefficients (1.54 and 1. 24). However, the maximal response estimated at 10 mM [Ca2+]o was larger than the maximal response at 2.5 mM [Ca2+]o. Increasing Ca influx through voltage-gated Ca channels and the resulting rise in the intracellular Ca2+ concentration had no effects on IGABA. However, IGABA was inhibited by extracellular divalent cations, with the following order of the inhibitory potency: Zn2+ > Ni2+ > Cd2+ > Co2+. The inhibitory action of Zn2+ on the [Ca2+]o-dependent IGABA increase was noncompetitive. The action of [Ca2+]o on IGABA was mimicked by Ba2+ or Sr2+. These results demonstrate that the extracellular domain of GABAC receptors has two functionally distinct binding sites represented by Ca2+ (facilitation) and Zn2+ (inhibition). Since [Ca2+]o and [Zn2+]o change into the opposite direction by light, it seems likely that they modify cooperatively the efficacy of the positive feedback consisting of the GABAC receptor.
Kaneda
M
M
Department of Physiology, Keio University School of Medicine, Tokyo 160, Japan. mkaneda@mc.med.keio.ac.jp
Mochizuki
M
M
Aoki
K
K
Kaneko
A
A
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002397:Catfishes / Q000502:physiology*; D002413:Cations, Divalent / Q000378:metabolism / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D018079:Receptors, GABA / Q000502:physiology*; D012160:Retina / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D002413:Cations, Divalent; C087200:GABA-C receptor; D018079:Receptors, GABA; D002104:Cadmium; D003035:Cobalt; D005680:gamma-Aminobutyric Acid; D009532:Nickel; D015032:Zinc; D002118:Calcium