Quisqualate- and kainate-activated channels in mouse central neurones in culture

Abstract

1. Quisqualate- and kainate-induced currents were recorded in mouse central neurones in culture, using both 'whole-cell' and 'outside-out' configurations. Experiments were made at room temperature. 2. Both quisqualate- and kainate-induced currents invert at 0 mV when the extracellular and intracellular solutions contain similar concentrations of monovalent cations. The changes of reversal potential produced by changes in the monovalent cation concentrations are consistent with the hypothesis that both agonists activate channels selectively permeable to cations. 3. The spectral analysis of the quisqualate- and kainate-induced currents recorded in the whole-cell mode indicates that the main component of the quisqualate noise has a time constant of 10-15 ms while the main component of the kainate noise has a time constant of 2-3 ms. 4. In outside-out patches most of the quisqualate-induced current was carried by channels with a conductance of about 8 pS. A small fraction of the quisqualate-induced current appears to be carried by two other channels: the 'NMDA channel' (40-50 pS) (Ascher, Bregestovski & Nowak, 1988) and a 'fast' channel, with a conductance of 15-35 pS, which was not activated by low concentrations of L-glutamate or by NMDA (N-methyl-D-aspartate). 5. Most of the kainate-induced current can be attributed to a channel characterized by a conductance of about 4 pS. Here again, outside-out patches revealed the presence of an additional channel, with a conductance of about 20 pS. 6. The results are consistent with the notion that there are at least three distinct receptors for excitatory amino acids, each preferentially activated by either NMDA, quisqualate or kainate, each opening channels with multiple conductance states. Other possibilities are discussed.