Single-channel currents of NMDA type activated by L- and D-Homocysteic acid in cerebellar granule cells in culture

The whole-cell and the outside-out configurations of the patch-clamp technique were used to study macroscopic and single-channel currents evoked by the enantiomers of homocysteic acid, the sulphur containing analogue of glutamate, in cerebellar granule cells in culture. L-Homocysteic acid (L-HC, 15-mu-M) and D-homocysteic acid (D-HC, 50-mu-M) induced whole-cell currents of comparable amplitude, that were abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP-5) (20-mu-M). AMPA (100-mu-M) induced whole-cell currents which were not modified by AP-5 (20-mu-M) but were blocked by CNQX. In the outside-out configuration, both L-HC and D-HC (15-mu-M) elicited single-channel currents. of the same conductance, mean open time and reversal potential as the NMDA-induced single-channel events. In the presence of Mg2+ (2 mM), D- and L-HC-induced single-channel currents were voltage-dependent. These data suggest that in cerebellar granule cells in culture, both L-HC and D-HC activate the same NMDA receptor channel complex.