Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells

Abstract

Depolarizing bipolar cells (DBCs) of the retina are the only neurons in the vertebrate central nervous system known to be hyperpolarized by the neurotransmitter glutamate. Both glutamate and its analogue L-2-amino-4-phosphonobutyrate (APB) hyperpolarize DBCs by decreasing membrane conductance. Furthermore, glutamate responses in DBCs slowly decrease during whole-cell recording, suggesting that the response involves a second messenger system. Here we report that intracellular cyclic GMP or GTP activates a membrane conductance that is suppressed by APB, resulting in an enhanced APB response. In the presence of GTP-gamma-S, APB causes an irreversible suppression of the conductance. Inhibitors of G-protein activation or phosphodiesterase activity decrease the APB response. Thus, the DBC glutamate receptor seems to close ion channels by increasing the rate of cGMP hydrolysis by a G protein-mediated process that is strikingly similar to light transduction in photoreceptors.

Synaptic transmission at retinal ribbon synapses

“…In fact, quantal miniature EPSCs have been detected in OFF bipolar cells and uncoupled horizontal cells (Hirasawa et al, 2001a;Kawai, 1999;Maple et al, 1994). Noise analysis also suggests an underlying quantal structure to ON bipolar cell responses , although discrete miniature EPSCs in this cell type are obscured by the slow kinetics of the mGluR6 transduction cascade (Nawy and Jahr, 1990). …”

Regulation of ON bipolar cell activity

“…Early studies of the glutamate receptor expressed by ON bipolar cells in lower vertebrates revealed that it possessed a novel pharmacological profile, as it was activated by L-2-amino-4-phosphonobutyric acid (L-AP4), and that activation of the receptor was associated with a conductance decrease (Shiells et al, 1981;Slaughter and Miller, 1981). Measurements of the current-voltage relation associated with the response to L-AP4 and to light demonstrated that both L-AP4 and the endogenous photoreceptor transmitter closed a channel with a reversal potential near 0 mV (Nawy and Copenhagen, 1987;Nawy and Jahr, 1990a). Furthermore, patch clamp experiments in which GTP analogs were dialyzed into ON bipolar cells demonstrated that the as yet unidentified receptor operated via a G protein-coupled mechanism (Nawy and Jahr, 1990a).…”

“…Measurements of the current-voltage relation associated with the response to L-AP4 and to light demonstrated that both L-AP4 and the endogenous photoreceptor transmitter closed a channel with a reversal potential near 0 mV (Nawy and Copenhagen, 1987;Nawy and Jahr, 1990a). Furthermore, patch clamp experiments in which GTP analogs were dialyzed into ON bipolar cells demonstrated that the as yet unidentified receptor operated via a G protein-coupled mechanism (Nawy and Jahr, 1990a). Several years later, the receptor was cloned and termed mGluR6 (Nakajima et al, 1993), a member of the group III family of metabotropic glutamate receptors.…”

Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retina

“…Therefore, we asked whether CB3a and CB3b could represent two subtypes of CBCs with opposite light response polarity. To address this question, we first examined their responses to L-AP4 (Slaughter & Miller 1981;Nawy & Jahr, 1990). Application of L-AP4 (50 μM) was found to reduce the steady inward current in both CB3a (n = 4) and CB3b (n = 7) ( Figures 5A and B), suggesting that metabotropic glutamate receptors are present in both groups of CBCs.…”