Activation of glutamate transporters in rods inhibits presynaptic calcium currents
We found that L-glutamate (L-Glu) inhibits L-type Ca2+ currents (ICa) 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 ICa by [similar]20% at 0.1 mM and [similar]35% at 1 mM. L-Glu also produced an inward current that reversed around ECl. The metabotropic glutamate receptor (mGluR) agonists t-ADA (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on ICa. 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 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 ICa. In summary, the results indicate that activation of glutamate transporters inhibits ICa 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.(Received April 14 2003)
(Accepted August 28 2003)
Key Words: Photoreceptor; L-type calcium channel; Retina; Glutamate transporter; Tiger salamander.
c1 Address correspondence and reprint requests to: Wallace B. Thoreson, Ophthalmology Department, University of Nebraska Medical Center, 985540 Nebraska Medical Center, Omaha, NE 68198-5540, USA. E-mail: WBTHORES@UNMC.EDU
p1 On leave from the Department of General Zoology and Neurobiology, University of Pécs, Pécs, Hungary