Activation of metabotropic glutamate receptors modulates the voltage-gatedsustained calcium current in a teleost horizontal cell

In the teleost retina, cone horizontal cells contain a voltage-activated su stained calcium current, which has been proposed to be involved in visual p rocessing. Recently, several studies have demonstrated that modulation of v oltage-gated channels can occur through activation of metabotropic glutamat e receptors (mGluRs). Because glutamate is the excitatory neurotransmitter in the vertebrate retina, we have used whole cell electrophysiological tech niques to examine the effect of mGluR activation on the sustained voltage-g ated calcium current found in isolated cone horizontal cells in the catfish retina. In pharmacological conditions that blocked voltage-gated sodium an d potassium channels, as well as N-methyl-D-aspartate (NMDA) and non-NMDA c hannels, application of L-glutamate or 1-aminocyclo-pentane-1,3-dicarboxyli c acid (1S,3R-ACPD) to voltage-clamped cone horizontal cells acted to incre ase the amplitude of the calcium current, expand the activation range of th e calcium current by 10 mV into the cell's physiological operating range, a nd shift the peak calcium current by -5 mV. To identify and characterize th e mGluR subtypes found on catfish cone horizontal cells, agonists of group I, group II, or group III mGluRs were applied via perfusion. Group I and gr oup III mGluR agonists mimicked the effect of L-glutamate or 1S,3R-ACPD, wh ereas group II mGluR agonists had no effect on L-type calcium current activ ity. Inhibition studies demonstrated that group I mGluR antagonists signifi cantly blocked the modulatory effect of the group I mGluR agonist, (S)-3,5- dihydroxyphenylglycine. Similar results were obtained when the group LU mGl uR agonist, L-2-amino-4-phosphonobutyric acid, was applied in the presence of a group III mGluR antagonist. These results provide evidence for two gro ups of mGluR subtypes on catfish cone horizontal cells. Activation of these mGluRs is linked to modulation of the voltage-gated sustained calcium curr ent.