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 similar to20% 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 ICa. D-aspartate (D-Asp), a glutamate transporter substrate, also inhibited ICa With significantly more inhibition at I 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.