Group III Metabotropic Glutamate Receptors and Exocytosed Protons Inhibit L-Type Calcium Currents in Cones But Not in Rods

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Abstract
Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist,l-2-amino-4-phosphonobutyric acid (l-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons.l-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition ofICawas most prominent around the physiological range of cone membrane potentials. In contrast,l-AP-4 did not affect L-typeICain rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed thatl-AP-4 inhibited bothICaand glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibitedICain cones but not in rods. Selective modulation ofICain cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.