Dd. Fraser et Ba. Macvicar, CHOLINERGIC-DEPENDENT PLATEAU POTENTIAL IN HIPPOCAMPAL CA1 PYRAMIDAL NEURONS, The Journal of neuroscience, 16(13), 1996, pp. 4113-4128
Cholinergic stimulation of the hippocampal formation results in excita
tion and/or seizure. We report here, using whole-cell patch-clamp tech
niques in the hippocampal slice (34-35 degrees C), a cholinergic-depen
dent slow afterdepolarization (sADP) and long-lasting plateau potentia
l (PP). In the presence of 20 mu M carbachol, action potential firing
evoked by weak intracellular current injection elicited an sADP that l
asted several seconds. Increased spike firing evoked by stronger depol
arizing stimuli resulted in long-duration PPs maintained close to -20
mV. Removal of either Na+ or Ca2+ from the external media, intracellul
ar Ca2+ ([Ca2+](i)) chelation with 10 mM bis(2- aminophenoxy)ethane-N,
N,N',N'-tetra-acetic acid, or the addition of 100 mu M Cd2+ to the per
fusate abolished both the sADP and PP. The sADP was depressed and the
PP was abolished by either 10 mu M nimodipine or 1 mu M omega-conotoxi
n, whereas 1.2 mu M tetrodotoxin was ineffective. The involvement of a
Na+/Ca2+ exchanger was minimal because both the sADP and PP persisted
after equimolar substitution of 50 mM Li+ for Na+ in the external med
ia or reduction of the bath temperature to 25 degrees C. Finally, in t
he absence of carbachol the sADP and PP could not be evoked when K+ ch
annels were suppressed, suggesting that depression of K+ conductances
alone was not sufficient to unmask the conductance. Based on these dat
a, we propose that a Ca2+-activated nonselective cation conductance wa
s directly enhanced by muscarinic stimulation. The sADP, therefore, re
presents activation of this conductance by residual [Ca2+](i), whereas
the PP represents a novel regenerative event involving the interplay
between high-voltage-activated Ca2+ channels and the Ca2+-activated no
nselective cation conductance. This latter mechanism may contribute si
gnificantly to ictal depolarizations observed during cholinergic-induc
ed seizures.