RECTIFICATION PROPERTIES AND CA2-RECEPTOR CHANNELS IN HIPPOCAMPAL CELLS( PERMEABILITY OF GLUTAMATE)

Excitatory amino acids exert a depolarizing action on central nervous system cells through an increase in cationic conductances. Non-NMDA re ceptors have been considered to be selectively permeable to Na+ and K, while Ca2+ influx has been thought to occur through the NMDA recepto r subtype. Recently, however, the expression of cloned non-NMDA recept or subunits has shown that lpha-amino-3-hydroxy-5-methyl-4-isoxazolepr opionic acid (AMPA) receptors are permeable to Ca2+ whenever the recep tor lacks a particular subunit (edited GluR-B). The behaviour of recom binant glutamate receptor channels predicts that Ca2+ would only perme ate through receptors that show strong inward rectification and vice v ersa, i.e. AMPA receptors with linear current-voltage relationships wo uld be impermeable to Ca2+. Using the whole-cell configuration of the patch-clamp technique, we have studied the Ca2+ permeability and the r ectifying properties of AMPA receptors, when activated by kainate, in hippocampal neurons kept in culture or acutely dissociated from differ entiated hippocampus. Cells were classified according to whether they showed outward rectifying (type I), inward rectifying (type II) or alm ost linear (type III) current-voltage relationships for kainate-activa ted responses. AMPA receptors of type I cells (52.2%) were mostly Ca2-impermeable (P-Ca/P-Cs = 0.1), while type II cells (6.5%) expressed C a2+-permeable receptors (P-Ca/P-Cs = 0.9). Type III cells (41.3%) show ed responses with low but not negligible Ca2+ permeability (P-Ca/P-Cs = 0.18). The degree of Ca2+ permeability and inward rectification were well correlated in cultured cells, i.e. more inward rectification cor responded to higher Ca2+ permeability. In acutely dissociated neurons, the restricted activation of the receptors located either in dendriti c or somatic membranes revealed that inward rectifying (i.e. Ca2+-perm eable) AMPA receptors are preferentially located in the dendritic shaf t (i.e. synaptic field). Our results indicate that oligomeric AMPA rec eptors of different subunit composition are coexpressed in dissimilar proportions in different cells, which would explain the incomplete inw ard rectification and graded Ca2+ permeability. In addition, Ca2+-perm eable AMPA receptors may exhibit non-homogeneous subcellular distribut ion.