The synaptic current at the rat ganglionic synapse and its interactions
with the neuronal voltage-dependent currents.
Oscar SACCHI, Maria Lisa ROSSI, Rita CANELLA, and Riccardo FESCE.
Department of Biology,Section of General Physiology, University of Ferrara,
Via Borsari 46, 44100 Ferrara, Italy and "Bruno Ceccarelli" Center, CNR Center
of Cytopharmacology and DIBIT Hospital San Raffaele, 20132 Milan, Italy.
APStracts 4:274N, 1997.
ABSTRACT
The membrane current activated by fast nicotinic excitation of intact and
mature rat sympathetic neurons was studied at 37øC, using the two-
microelectrode voltage-clamp technique. The EPSC was modeled as the difference
between two exponentials. A fast time constant (_2; mean value 0.57 ms), which
proves to be virtually voltage-independent, governs the current rise phase,
while a longer time constant (_1; range 5.2 - 6.8 ms in 2mM-Ca2+)
describes the current decay and shows a small negative voltage dependence. A
mean peak synaptic conductance of 0.58 æS per neuron is measured following
activation of the whole presynaptic input in 5mM-Ca2+ external solution
(0.40 æS in 2mM-Ca2+). The miniature EPSCs also rise and decay with
exponential time constants very similar to those of the compound EPSC recorded
at the same voltage. A mean peak conductance of 4.04 nS is estimated for the
unitary event. Deconvolution procedures were employed to decompose evoked
macrocurrents. It is shown that under appropriate conditions the duration of
the driving function describing quantal secretion can be reduced to less than
one millisecond. The shape of the EPSC is accurately mimicked by a complete
mathematical model of the sympathetic neuron incorporating the kinetic
properties of five different voltage-dependent current types, which were
characterized in a previous work. We show that IA channels are opened by
depolarizing voltage steps or by synaptic potentials in the subthreshold
voltage range, provided that the starting holding voltage is sufficiently
negative to remove IA steady-state inactivation (<-50?mV) and the
voltage trajectories are sufficiently large to enter the IA activation range
(>-65?mV). Under current-clamp conditions this gives rise to an additional
fast component in the early phase of membrane repolarization _ in response to
voltage pulses _ and to a consistent distortion of the EPSP time course around
its peak _ in response to the synaptic signal. When the stimulation initiates
an action potential, IA is shown to significantly increase the synaptic
threshold conductance (up to a factor of 2 when IA is fully deinactivated),
compared with that required when IA is omitted. The voltage dependence of this
effect is consistent with the IA steady-state inactivation curve. It is
concluded that IA, in addition to speeding up the spike repolarization
process, also shunts the excitatory drive and delays or prevents the firing of
the neuron action potential.
Received 18 February 1997; accepted in final form 24 September 1997.
APS Manuscript Number J141-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997