The Journal of Neurophysiology Vol. 87 No. 1 January 2002, pp. 250-256
Copyright ©2002 by the American Physiological Society
Morphological and Electrophysiological Evidence for an Ionotropic
GABA Receptor of Novel Pharmacology
D.-W.
Shen,1
M. H.
Higgs,1
D.
Salvay,1
J. W.
Olney,2
P. D.
Lukasiewicz,1,3 and
C.
Romano1,3
1Department of Ophthalmology and Visual
Science, 2Department of Psychiatry, and
3Department of Anatomy and Neurobiology,
Washington University School of Medicine, St. Louis, Missouri 63110
Shen, D.-W.,
M. H. Higgs,
D. Salvay,
J. W. Olney,
P. D. Lukasiewicz, and
C. Romano.
Morphological and Electrophysiological Evidence for an Ionotropic
GABA Receptor of Novel Pharmacology. J. Neurophysiol. 87: 250-256, 2002. Evidence from toxicological
studies suggested that an ionotropic GABA receptor of novel
pharmacology (picrotoxin-insensitive, bicuculline-sensitive) exists in
the chick embryo retina. In this report, we provide direct
morphological and electrophysiological evidence for the existence of
such an iGABA receptor. Chick embryo retinas (14-16 days old)
incubated in the presence of kainic acid showed pronounced
histopathology in all retinal layers. Maximal protection from this
toxicity required a combination of bicuculline and picrotoxin.
Individual application of the antagonists indicated that a
picrotoxin-insensitive, bicuculline-sensitive GABA receptor is likely
to be present on ganglion and amacrine, but not bipolar, cells. GABA
currents in embryonic and mature chicken retinal neurons were measured
by whole cell patch clamp. GABA was puffed at the dendritic processes
in the IPL. Picrotoxin (500 µM, in the bath) eliminated all (>95%)
the GABA current in the majority of ganglion and amacrine cells tested,
but many cells possessed a substantial picrotoxin-insensitive
component. This current was eliminated by bicuculline (200 µM). This
current was not a transporter-associated current, since it was not
altered by GABA transport blockers or sodium removal. The
current-voltage relation was linear and reversed near
ECl, as expected for a ligand-gated chloride
current. Both pentobarbital and lorazepam enhanced the
picrotoxin-insensitive current. We conclude that chicken retinal
ganglion and amacrine cells express a GABA receptor that is
GABA-A-like, in that it can be blocked by bicuculline, and positively
modulated by barbiturates and benzodiazepines, but is insensitive to
the noncompetitive blocker picrotoxin. Understanding the molecular
properties of this receptor will be important for understanding both
physiological GABA neurotransmission and the pathology of GABA receptor overactivation.
