Activation of glutamate transporters in rods inhibits presynaptic calcium currents

We found that L-glutamate (L-Glu) inhibits L-type Ca²⁺ currents (I_Ca) in rod photoreceptors. This inhibition was studied in isolated rods or rods in retinal slices from tiger salamander using perforated patch whole cell recordings and Cl^-imaging techniques. Application of L-Glu inhibited I_Ca by ∼20% at 0.1 mM and ∼35% at 1 mM. L-Glu also produced an inward current that reversed around E_Cl. The metabotropic glutamate receptor (mGluR) agonists t-ADA (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on I_Ca. However, the glutamate transport inhibitor, TBOA (0.1 mM), prevented L-Glu from inhibiting I_Ca. D-aspartate (D-Asp), a glutamate transporter substrate, also inhibited I_Ca with significantly more inhibition at 1 mM than 0.1 mM. Using Cl^- imaging, L-Glu (0.1-1 mM) and D-Asp (0.1-1 mM) were found to stimulate a Cl^- efflux from terminals of isolated rods whereas the ionotropic glutamate receptor agonists NMDA, AMPA, and kainate and the mGluR agonist, 1S,3R-ACPD, did not. Glutamate-evoked Cl^- effluxes were blocked by the glutamate transport inhibitors TBOA and DHKA. Cl ^- efflux inhibits Ca²⁺ channel activity in rod terminals (Thoreson et al. (2000), Visual Neuroscience 17, 197). Consistent with the possibility that glutamate-evoked Cl^- efflux may play a role in the inhibition, reducing intraterminal Cl^- prevented L-Glu from inhibiting I_Ca. In summary, the results indicate that activation of glutamate transporters inhibits I_Ca in rods possibly as a consequence of Cl^- efflux. The neurotransmitter L-Glu released from rod terminals might thus provide a negative feedback signal to inhibit further L-Glu release.