The Journal of Neurophysiology Vol. 78 No. 5 November 1997, pp. 2402-2412
Copyright ©1997 The American Physiological Society

GABA Receptors of Bipolar Cells From the Skate Retina: Actions of Zinc on GABA-Mediated Membrane Currents

Haohua Qian^{1, 2}, Lihong Li^{1, 4}, Richard L. Chappell^{1, 4}, and Harris Ripps^{1, 3}

¹ The Marine Biological Laboratories, Woods Hole, Massachusetts 02543; ² Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; ³ Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, Illinois 60612; and ⁴ Department of Biological Sciences, Hunter College and Graduate School, City University of New York, New York 10021

Qian, Haohua, Lihong Li, Richard L. Chappell, and Harris Ripps. GABA receptors of bipolar cells from the skate retina: actions of zinc on GABA-mediated membrane currents. J. Neurophysiol. 78: 2402-2412, 1997. -Aminobutyric acid (GABA)-induced currents were recorded from isolated bipolar cells of the skate retina using perforated patch-clamp methodology. Pharmacological analysis of the responses, using selective agonists and antagonists of the major classes of GABA receptor, revealed the presence of both GABA_A and GABA_C receptors at both the dendrites and axon terminals of the bipolar cells. The two receptor types showed very different reactions to zinc, a divalent metallic cation that was detected in the synaptic terminal region of skate photoreceptors. Currents mediated by the activation of GABA_C receptors were down-regulated by zinc, a feature that is typical of the action of zinc on GABA_C receptors. On the other hand, the effects of zinc on GABA_A receptor-mediated activity was highly dependent on zinc concentration. Unlike theGABA_A receptors on other neurons, responses mediated by activation of the GABA_A receptor of skate bipolar cells were significantly enhanced by zinc concentrations in the range of 0.1-100 µM; at higher concentrations of zinc (>100 µM), response amplitudes were suppressed below control levels. The enhancement of GABA_A receptor activity on skate bipolar cells showed little voltage dependence, suggesting that zinc is acting on the extracellular domain of the GABA_A receptor. In the presence of 10 µM zinc, the dose-response curve for 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; a GABA_A agonist that suppresses GABA_C-activated currents) was shifted to the left of the curve obtained in the absence of zinc, but without a significant change in the response maximum. This finding indicates that the enhancing effect of zinc is due primarily to its ability to increase the sensitivity of the GABA_A receptor. The novel enhancement of neuronal GABA_A receptor activity by zinc, observed previously in the GABA_A-mediated responses of skate Müller (glial) cells, may reflect the presence of a unique subtype of GABA_A receptor on the bipolar and Müller cells of the skate retina.

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