The Journal of Neurophysiology Vol. 84 No. 2 August 2000, pp. 771-779
Copyright ©2000 by the American Physiological Society
Postsynaptic Receptor Occupancy During Evoked Transmission at
Striatal GABAergic Synapses In Vitro
Eva
Rumpel and
Jan C.
Behrends
Department of Physiology, University of Munich, 80336 Munich,
Germany
Rumpel, Eva and
Jan C. Behrends.
Postsynaptic Receptor Occupancy During Evoked Transmission at
Striatal GABAergic Synapses In Vitro. J. Neurophysiol. 84: 771-779, 2000. The effect of benzodiazepines
(BZs) on GABAA-ergic synaptic responses depends
on the control receptor occupancy: the BZ-induced enhancement of
receptor affinity can lead to greater peak amplitudes of quantal
responses only when, under normal conditions, receptors are not fully
saturated at peak. Based on this fact, receptor occupancy at the peak
of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) has
been assessed in various mammalian neuronal preparations. To use the
same principle with compound (or multiquantal), action
potential-evoked IPSCs, complications introduced by quantal asynchrony
in conjunction with the BZ-induced increase in the decay time of the
quantal responses have to be overcome. We used a simple analytic
convolution model to calculate expected changes in the rise time and
amplitude of postsynaptic currents when the decay time constant, but
not the peak amplitude, of the underlying quantal responses is
increased, this being the expected BZ effect at saturated synapses.
Predictions obtained were compared with the effect of the BZ
flunitrazepam on IPSCs recorded in paired pre- and postsynaptic whole
cell voltage-clamp experiments on striatal neurons in cell culture. In
22 pairs, flunitrazepam (500 nM) reliably prolonged the decay of IPSCs
(49 ± 19%, mean ± SE) and in 18 of 22 cases produced an
enhancement in their peak amplitude that varied markedly between 3 and
77% of control (26.0 ± 5.3%). The corresponding change in rise
time, however (+0.38 ± 0.11 ms, range 
0.8 to +1.3 ms) was far
smaller than calculated for the observed changes in peak amplitude
assuming fixed quantal size. Because therefore an increase in quantal
size is required to explain our findings, postsynaptic
GABAA receptors were most likely not saturated
during impulse-evoked transmission at these unitary connections. The
peak amplitudes of miniature IPSCs in these neurons were also increased
by flunitrazepam (500 nM, +26.8 ± 6.6%), and their decay time
constant was increased by 26.3 ± 7.3%. Using these values in our
model led to a slight overestimate of the change in compound IPSC
amplitude (+28 to +30%).
