The mechanisms underlying the depression of evoked fast epscs following.
Tanaka, E., S. Yasumoto, G. Hattori, S. Niiyama, S. Matsuyama and H. Higashi.
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi,
Kurume, 830-0011 JAPAN
APStracts 8:0225J, 2001.
The mechanisms underlying the depression of evoked fast excitatory postsynaptic
currents (EPSCs) following superfusion with medium deprived of oxygen and glucose (in
vitro ischemia) for a 4 min period in hippocampal CA1 neurons were investigated in rat
brain slices. The amplitude of evoked fast EPSCs decreased by 85±7 % of the control 4
min after the onset of in vitro ischemia. In contrast, the exogenous glutamate-induced
inward currents were augmented, while the spontaneous miniature EPSCs obtained in the
presence of tetrodotoxin (TTX, 1 µM) did not change in amplitude during in vitro
ischemia. In a normoxic medium, a pair of fast EPSCs was elicited by paired-pulse
stimulation (40 msec interval), and the amplitude of the second fast EPSC increased to
156±24 % of the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio)
increased during in vitro ischemia. Pretreatment of the slices with adenosine 1 (A1)
receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the depression of the
fast EPSCs, in a concentration-dependent manner: in the presence of 8-CPT (1-10 µM),
the amplitude of the fast EPSCs decreased by only 20 % of the control during in vitro
ischemia. In addition, 8-CPT antagonized the enhancement of the PPF ratio during in
vitro ischemia. A pair of presynaptic volleys and excitatory postsynaptic field potentials
(fEPSPs) were extracellularly recorded in a proximal part of the stratum radiatum in the
CA1 region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On
the other hand, the amplitudes of the first and second presynaptic volley, which were
abolished by TTX (0.5 µM), did not change during in vitro ischemia. The maximal slope
of the Ca2+-dependent action potential of the CA3 neurons, which were evoked in the
presence of 8-CPT (1 µM), nifedipine (20 µM), TTX (0.5 µM) and tetraethyl ammonium
chloride (20 mM), decreased by 12±6 % of the control 4 min after the onset of in vitro
ischemia. These results suggest that in vitro ischemia depresses the evoked fast EPSCs
mainly via the presynaptic A1 receptors, and the remaining 8-CPT-resistant depression of
the fast EPSCs is probably due to a direct inhibition of the Ca2+ influx to the axon
terminals.
Received 29 December 2000; accepted in final form 25 May 2001
APS Manuscript Number J934-0.
Article publication pending Am J Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 31 July 2001