Putative GABAergic mechanisms were studied in the cat retina by exogen
ous application of the GABA, antagonists picrotoxin (PTX), native bicu
culline (BCC), and bicuculline methyl bromide (BCC MeBr). When recordi
ng intracellular responses from horizontal cells (HCs) and amacrine ce
lls as well as electroretinograms (ERGs), drugs were added to the perf
usate used to maintain the isolated eyecup; when recording extracellul
ar spikes from ganglion cells of anesthetized cats, drugs were introdu
ced by iontophoretic injection. Both PTX and BCC MeBr had relatively l
ittle influence upon the response properties of HCs. In contrast, nati
ve BCC tended to decrease the amplitude of and to slow the photic resp
onse to light onset and both to quicken and to increase the amplitude
of response to light offset; in the presence of native BCC, HC respons
es were dominated by a prominent spike-like ''Off-overshoot.'' The inf
luence of GABA(A) agonists upon HC responses was not blocked by GABA(A
) antagonists. ERG b-wave amplitude was reduced both by PTX and by nat
ive BCC, but was not influenced by BCC MeBr. Latency (time to half-pea
k) was increased by low doses of native BCC, and to a lesser extent PT
X but not BCC MeBr. Rod-amacrine On-transient responses were increased
in amplitude by PTX. Extracellular recordings from On- and Off-X and
Y ganglion cell types became considerably more transient with applicat
ion of either PTX, native BCC, or BCC MeBr this tendency was greater i
n Off-type ganglion cells. Collectively, these results strengthen conc
lusions from the previous paper suggesting that GABA serves to stow on
set and offset kinetics of retinal neurons, making them more sustained
and less phasic. They also suggest that in mammalian retina heterogen
eous types of GABA, receptors exist, segregated into different zones:
a distal zone, sensitive only to native BCC, a central zone sensitive
to both native BCC and PTX, and a proximal zone sensitive to native BC
C, BCC methyl halides (BCC MeH), and PTX. Only the proximal zone obeys
conventional GABA(A) pharmacology.