J. Lerma et al., RECTIFICATION PROPERTIES AND CA2-RECEPTOR CHANNELS IN HIPPOCAMPAL CELLS( PERMEABILITY OF GLUTAMATE), European journal of neuroscience, 6(7), 1994, pp. 1080-1088
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.