The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 2159-2165
Copyright ©2001 by the American Physiological Society
Muscarinic Depression of Synaptic Transmission in the
Epileptogenic GABA Withdrawal Syndrome Focus
C.
Silva-Barrat,
M.
Szente,
Ch.
Menini,
J. C.
Velluti, and
J.
Champagnat
Laboratoire de Génétique de la Neurotransmission et des
Processus Neurodégénératifs, Unité Mixte de
Recherche 9923, Centre National de la Recherche Scientifique, 75634 Paris, France
Silva-Barrat, C.,
M. Szente,
Ch. Menini,
J. C. Velluti, and
J. Champagnat.
Muscarinic Depression of Synaptic Transmission in the
Epileptogenic GABA Withdrawal Syndrome Focus. J. Neurophysiol. 85: 2159-2165, 2001. The GABA withdrawal syndrome
(GWS) is a model of local status epilepticus consecutive to the
interruption of a prolonged GABA infusion into the rat somatomotor
cortex. Bursting patterns in slices from GWS rats include intrinsic
bursts of action potentials (APs) induced by intracellular depolarizing
current injection and/or paroxysmal depolarization shifts (PDSs)
induced by white matter stimulation. Possible changes in the effects of
cholinergic drugs after in vivo induction of GWS were investigated on
bursting cells (n = 30) intracellularly recorded in
neocortical slices. In GWS slices, acetylcholine (Ach, 200-1000 µM)
or carbachol (Cch, 50 µM) applications increased the number of bursts
induced by depolarizing current injection while synaptically induced
PDSs were significantly diminished (by 50-60%) or even blocked
independently of the cholinergic-induced depolarization. The intrinsic
burst facilitation and PDS depression provoked by Ach or Cch were
mimicked by methyl-acetylcholine (mAch, 100-400 µM,
n = 11), were reversed by atropine application
(1-50 µM, n = 3), and were not mimicked by
nicotine (50-100 µM, n = 4), indicating the
involvement of muscarinic receptors. In contrast, in nonbursting cells
from the same epileptic area (n = 42) or from
equivalent area in control rats (n = 24), a
nonsignificant muscarinic depression of EPSPs was induced by Cch and
Ach. The mAch depression of excitatory postsynaptic potential (EPSPs)
was significantly lower than that seen for PDSs in GWS rats. None of
the cholinergic agonists caused bursting appearance in these cells.
Therefore the present study demonstrates a unique implication of
muscarinic receptors in exerting opposite effects on intrinsic membrane
properties and on synaptic transmission in epileptiform GWS. Muscarinic
receptor mechanisms may therefore have a protective role against the
development and spread of epileptiform activity from the
otherwise-activated epileptic focus.
