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Journal of Neuroscience, Vol 15, 2668-2679, Copyright © 1995 by Society for Neuroscience
Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals
ZH Pan and SA Lipton
Department of Neurology, Children's Hospital, Boston, Massachusetts, USA.
Inhibitory effects of GABA on K(+)-evoked Ca2+ influx into rat retinal
bipolar cell terminals were studied using calcium imaging methods.
Application of high K+ evokes a sustained, reversible increase in [Ca2+]i
at bipolar cell terminals, which occurs mainly via
dihydropyridine-sensitive (L-type) Ca2+ channels. There are at least two
GABA receptor subtypes coexisting at bipolar cell terminals: a conventional
GABAA receptor and a bicuculline/baclofen-insensitive GABA receptor.
Activation of either GABA receptor inhibited the K(+)-evoked Ca2+ response.
However, these two GABA receptor subtypes have distinct properties. GABAA
receptors suppress the Ca2+ response only at relatively high concentrations
of agonist, and with fas kinetics and a narrow dynamic range. In contrast,
the bicuculline/baclofen-insensitive GABA receptors produce inhibition on
the Ca2+ response at a much lower concentration of agonist, and with slow
onset and a wider dynamic range. The pharmacologic profile of the
bicuculline/baclofen- insensitive GABA receptor at bipolar cell terminals
is most similar to the GABAC receptor reported by Feigenspan et al. (1993).
Unlike the GABAC receptors described in other species, it is extremely
insensitive to picrotoxin. Therefore, it may be appropriate to refer to
this receptor as a picrotoxin-insensitive GABAc receptor. 3-
Aminopropyl(methyl)phosphinic acid (3-APMPA) and 3- aminopropylphosphonic
(3-APA), two phosphate analogs of GABA, selectively antagonize the
picrotoxin-insensitive GABAc receptors but not the GABAA receptors in this
system. These results imply a functional role for multiple GABA receptors
in regulating synaptic transmission at bipolar cell terminals.
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