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

Apr 22, 2005The Journal of neuroscience : the official journal of the Society for Neuroscience

Certain receptors and released protons reduce calcium currents in cone cells but not in rod cells

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Abstract

The group III metabotropic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP-4) inhibited both the steady and off-transient inward currents in OFF bipolar cells and horizontal cells.

L-AP-4 did not affect the glutamate-induced current in OFF bipolar cells and horizontal cells.
L-AP-4 inhibited the presynaptic L-type calcium current in cones by shifting the voltage dependence of activation to more positive membrane potentials.
The inhibition of calcium current was most pronounced around the physiological range of cone membrane potentials.
L-AP-4 did not affect the L-type calcium current in rods.
Paired recordings confirmed that L-AP-4 inhibited calcium current and glutamate release in cones but not in rods.
Exocytosed protons also inhibited calcium current in cones but not in rods.

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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 of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

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

Abstract

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