title: Co-expression of AMPA/kainate receptor-operated channels with high and low Ca2+ permeability in single rat retinal ganglion cells.
abstract: The patch-clamp technique was used to record whole-cell currents induced by alpha-amino-3-hydroxyl-5-methyl-isoxazol-4-propionic acid (AMPA) or kainate in solitary rat retinal ganglion cells (n = 125) in vitro. Two groups of retinal ganglion cells could be distinguished according to their responses to kainate or AMPA in extracellular solutions with Ca2+ as the only permeant cation. The ratio of the steady-state currents evoked by a given concentration of AMPA compared to kainate was low (0.08) in the first group and high (0.61) in the second group of retinal ganglion cells. The Ca2+ permeability through AMPA/kainate receptor-operated channels was low (PCa2+/PCs+ < 0.1) in the first group (n = 74, 59%) and moderate (PCa2+/PCs+ = 0.53) in the second group (n = 51, 41%) of retinal ganglion cells. The fraction of the total current induced by stimulation of non-N-methyl-D-aspartate receptors that is flowing through Ca2+ permeable AMPA/kainate channels in single cells with high Ca2+ permeability was estimated by comparing the current-voltage relationship in extracellular solutions with either Ca2+ or Na+ as the sole charge carrier. The contribution of Ca(2+)-permeable channels to the non-N-methyl-D-aspartate receptor induced whole-cell current in single Ca2+ permeable cells (n = 12) ranged from 40 to 70%, correlating with the intermediate level of Ca2+ permeability (PCa2+/PCs+ = 0.22-0.80) measured by an independent method in these cells. Thus, single Ca(2+)-permeable cells appear to express at least two types of AMPA/kainate receptor-operated channels with high or low Ca2+ permeability. Using the polymerase chain reaction, transcripts for the glutamate receptor subunits 1-4, including their "flip" and "flop" versions, were identified in retinal ganglion cells. Together, these findings suggest that among rat retinal ganglion cells there are differences in the pattern of expression of AMPA/kainate receptor-operated channels. Moreover, individual cells co-express multiple heterologous non-N-methyl-D-aspartate receptors with distinct functional properties. The functional diversity of these receptors may play an important role in controlling Ca2+ entry into neurons. We speculate that the low Ca2+ permeability and the preference for kainate in one group of retinal ganglion cells may be due to the predominant expression of non-N-methyl-D-aspartate receptors containing the edited form of the glutamate receptor subunit 2 flop splice variant.
mesh_terms: D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010539:Permeability; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D012313:RNA; D012194:RNA-Directed DNA Polymerase; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors