The GABA Receptors of Bipolar Cells from the Skate Retina: The Actions of
Zinc on GABA-mediated Membrane Currents
Haohua Qian, Lihong Li, Richard L. Chappell, and Harris Ripps.
The Marine Biological Laboratories, Woods Hole, MA, Department of Molecular
and Cellular Biology, Harvard University, Cambridge, MA 02138, Department of
Ophthalmology and Visual Sciences, University of Illinois College of Medicine,
Chicago, IL 60612, and the 4Department of Biological Sciences, Hunter College
and Graduate School, CUNY, New York, NY 10021.
APStracts 4:124N, 1997.
ABSTRACT
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 GABAA and GABAC 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 GABAC receptors were down-regulated by zinc, a
feature that is typical of the action of zinc on GABAC receptors. On the other
hand, the effects of zinc on GABAA receptor-mediated activity was highly
dependent upon zinc concentration. Unlike the GABAA receptors on other
neurons, responses mediated by activation of the GABAA receptor of skate
bipolar cells were significantly enhanced by zinc concentrations in the range
of 0.1 to 100 (M; at higher concentrations of zinc (> 100 (M), response
amplitudes were suppressed below control levels. The enhancement of GABAA
receptor activity on skate bipolar cells showed little voltage-dependence,
suggesting that zinc is acting on the extracellular domain of the GABAA
receptor. In the presence of 10 (M zinc, the dose-response curve for THIP (a
GABAA agonist that suppresses GABAC -activated currents) was shifted to 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 GABAA
receptor. The novel enhancement of neuronal GABAA receptor activity by zinc,
observed previously in the GABAA-mediated responses of skate Müller (glial)
cells, may reflect the presence of a unique subtype of GABAA receptor on the
bipolar and Müller cells of the skate retina.
Received 18 February 1996; accepted in final form 2 July 1997.
APS Manuscript Number J143-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 July 1997