Ta. Pitler et Be. Alger, DIFFERENCES BETWEEN PRESYNAPTIC AND POSTSYNAPTIC GABA(B) MECHANISMS IN RAT HIPPOCAMPAL PYRAMIDAL CELLS, Journal of neurophysiology, 72(5), 1994, pp. 2317-2327
1. Whole cell voltage-clamp techniques were used in the CAI region of
rat hippocampal slices to study presynaptic and postsynaptic gamma-ami
nobutyric acid B (GABA(B)) response mechanisms. The effects of the pro
tein kinase C activator phorbol 12,13-diacetate (PDA),barium (Ba2+), a
nd pertussis toxin were compared on the presynaptic and postsynaptic G
ABA(B) actions of bath-applied baclofen and paired-pulse depression (P
PD) of the monosynaptic GABA(A) inhibitory postsynaptic current (IPSC)
. The magnitude of PPD was dependent on the amplitude of the first res
ponse. PPD was predominantly a GABA(B)-mediated effect, as it was very
much reduced by the GABA(B) antagonist CGP 35348. 2. PDA enhanced mon
osynaptic GABA(A) IPSCs through an apparently presynaptic mechanism. I
ontophoretic GABA(A) responses were unaffected, and there was no chang
e in E(IPSC). PDA increased the frequency of spontaneous, tetrodotoxin
-insensitive IPSCs without significantly affecting their amplitudes. T
he inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA
application, stimulus intensity was adjusted to produce responses of c
omparable amplitude to control responses. PDA had a marked and reversi
ble depressant effect on the postsynaptic GABA(B) response and caused
a lesser, but still significant, reduction in the baclofen-induced red
uction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramat
ically reduced postsynaptic GABA(B) responses; it had no effect on PPD
. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs,
although this was not statistically significant. 4. Pertussis toxin,
injected 2-3 days earlier into the intact hippocampus, blocked all thr
ee GABA(B) responses equally (similar to 70% decrease). 5. We conclude
that presynaptic and postsynaptic GABA(B) mechanisms are mediated by
G proteins that couple to different mechanisms. Discrepancies with pre
vious work are evidently due to the use of different tissue preparatio
ns and different target responses. Even though protein kinase C activa
tion caused a partial reduction in the presynaptic effect of baclofen,
its lack of effect on PPD makes a significant role for protein kinase
C in modulation of PPD unlikely.