Hh. Qian et al., GABA RECEPTORS OF BIPOLAR CELLS FROM THE SKATE RETINA - ACTIONS OF ZINC ON GABA-MEDIATED MEMBRANE CURRENTS, Journal of neurophysiology, 78(5), 1997, pp. 2402-2412
gamma-Aminobutyric acid (GABA)-induced currents were recorded from iso
lated bipolar cells of the skate retina using perforated patch-clamp m
ethodology. Pharmacological analysis of the responses, using selective
agonists and antagonists of the major classes of GABA receptor, revea
led the presence of both GABA(A) and GABA(C) receptors at both the den
drites and axon terminals of the bipolar cells. The two receptor types
showed very different reactions to zinc, a divalent metallic cation t
hat was detected in the synaptic terminal region of skate photorecepto
rs. 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 the GABA(A) receptors on other neurons, responses mediated by
activation of the GABA(A) receptor of skate bipolar cells were signifi
cantly enhanced by zinc concentrations in the range of 0.1-100 mu M; a
t higher concentrations of zinc (>100 mu M), response amplitudes were
suppressed below control levels. The enhancement of GABA(A) receptor a
ctivity on skate bipolar cells showed little voltage dependence, sugge
sting that zinc is acting on the extracellular domain of the GABA(A) r
eceptor. In the presence of 10 mu M zinc, the dose-response curve for
4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; a GABA(A) agonis
t that suppresses GABA(C)-activated currents) was shifted to the left
of the curve obtained in the absence of zinc, but without a significan
t change in the response maximum. This finding indicates that the enha
ncing effect of zinc is due primarily to its ability to increase the s
ensitivity 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 Muller (glial) cells, may reflect the pres
ence of a unique subtype of GABA(A) receptor on the bipolar and Muller
cells of the skate retina.