Metabotropic
gamma-aminobutyric acid (
GABA) receptors were studied in amphibian retinal ganglion cells using whole cell current and voltage clamp techniques. The aim was to identify the types of receptor present and their mechanisms of action and modulation. Previous results indicated that
ganglion cells possess two ionotropic
GABA receptors: GABAAR and GABACR. This study demonstrates that they also possess two types of metabotropic GABAB receptor: one sensitive to
baclofen and another to cis-aminocrotonic
acid (
CACA). The effects of these selective agonists were blocked by
GDP-beta-S.
Baclofen suppressed an
omega-conotoxin-GVIA-sensitive
barium current, and this action was reversed by prepulse facilitation, indicative of a direct
G-protein pathway. The effect of
baclofen was also partially occluded by agents that influence the
protein kinase A (PKA) pathway. But the effect of PKA activation was unaffected by prepulse facilitation, indicating PKA acted through a parallel pathway.
Calmodulin antagonists reduced the action of
baclofen, whereas inhibitors of
calmodulin phosphatase enhanced it. Antagonists of internal
calcium release, such as
heparin and
ruthenium red; did not affect the
baclofen response. Thus, the
baclofen-sensitive receptor may respond to influx of
calcium. The
CACA-sensitive
GABA receptor reduced current through
dihydropyridine-sensitive channels.
Sodium nitroprusside and
8-bromo-cGMP enhanced the action of
CACA, indicating that a
nitric oxide system can up-regulate this receptor pathway.
CACA-sensitive and
baclofen-sensitive GABAB receptors reduced spike activity in
ganglion cells. Overall, retinal ganglion cells possess four types of
GABA receptor, two ionotropic and two metabotropic. Each has a unique electrogenic profile, providing a wide range of neural integration at the final stage of
retinal information processing.