Jm. Bekkers et al., DIFFERENTIAL-EFFECTS OF HISTAMINE ON THE N-METHYL-D-ASPARTATE CHANNELIN HIPPOCAMPAL SLICES AND CULTURES, Neuroscience, 72(3), 1996, pp. 669-677
The effect of histamine on N-methyl-D-aspartate currents was investiga
ted in pyramidal neurons in the CA1 region of acute hippocampal slices
from juvenile rats. The objective was to compare histamine effects in
the slice with those previously reported in acutely dissociated and c
ultured hippocampal neurons. Micromolar concentrations of histamine ha
d no effect on N-methyl-D-aspartate-mediated excitatory postsynaptic c
urrents in the slice, in contrast to the large enhancement seen in cul
ture under identical conditions. However, millimolar concentrations of
histamine blocked these currents both in the slice and in culture. Po
ssible reasons for the lack of enhancement in the slice were explored
as follows. (1) Histamine could not penetrate the slice or was already
present at high concentrations inside the dice. This was tested by re
cording N-methyl-D-aspartate currents elicited in outside-out patches
pulled from the somas of CA1 slice neurons. Histamine still had no eff
ect in patches, whereas the corresponding experiment for cultured neur
ons showed robust enhancement. (2) Slices release an endogenous ligand
that binds with high affinity to the histamine site on the N-methyl-D
-aspartate receptor, blocking its activation. This was tested by super
fusing cultures with supernatant from homogenized slice tissue. Histam
ine enhancement was maintained in these cultures. (3) CA1 dices and cu
ltures express different N-methyl-D-aspartate receptor subtypes. The r
everse transcription-polymerase chain reaction technique was used to e
xamine the expression of messenger RNA encoding N-methyl-D-aspartate r
eceptor subunits in the two systems. No difference was found in the wh
ole-tissue expression of messenger RNA for the NR2A, 2B or 2C subunits
or for the eight known splice variants of the NR1 subunit. It is hypo
thesized that the differential enhancing effect of histamine in slices
and culture involves posttranslational modifications or other factors
that modulate the N-methyl-D-aspartate receptor/ion channel according
to its environment.