Journal of Neurophysiology, Vol 69, Issue 2 432-441, Copyright © 1993 by APS

ARTICLES

Site of synaptic depression during hypoxia: a patch-clamp analysis

N. Hershkowitz, A. N. Katchman and S. Veregge
Department of Neurology, Georgetown University School of Medicine, Washington, DC 20007.

1. The effect of hypoxia on synaptic physiology was investigated in hippocampal slices from 16- to 23-day-old rats. CA1 pyramidal cells were examined by whole cell patch-clamp recording, and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebrospinal fluid (ACSF) to ACSF saturated with 95% N2-5%CO2. Synaptic responses were assessed by stimulating the Schaffer collateral-commissural projection with an electrode in the stratum radiatum every 20 s. 2. Within 100-200 s of the onset of hypoxia, the orthrodromically elicited synaptic response of the CA1 cells was largely inhibited. In addition, a slow inward current was observed after the onset of hypoxia. A transient outward current, preceding the inward current, was observed in only 2 of 17 cells examined. The slow inward current culminated in an irreversible rapid inward current at approximately 140 s after hypoxia. This rapid inward current occurred simultaneously with spreading depression as measured by field potentials. Tetrodotoxin (TTX) had no effect on the onset of this current, whereas kynurenic acid significantly delayed its occurrence. 3. Before the onset of hypoxia, spontaneous transient inward currents were apparent. The frequency of these events increased by three- to fourfold after hypoxia. The transient inward currents persisted in slices incubated in TTX, but were almost completely inhibited in slices incubated with the mixed N-methyl-D-aspartate (NMDA)/non-NMDA antagonist kynurenic acid. This identified the spontaneous events that were increased in frequency by hypoxia as glutamatergic miniature excitatory postsynaptic currents (mEPSCs). 4. The mean amplitude of the mEPSCs was not affected by hypoxia at a time at which the orthodromically elicited synaptic response was almost completely inhibited by hypoxia. In addition, the response of the postsynaptic cell to pressure ejection of glutamate was not inhibited under conditions of nearly complete blocked the synaptic response. Thus, by two measures, the postsynaptic response was not affected by hypoxia, indicating that the site of hypoxia-induced synaptic failure was at the presynaptic terminal. 5. The orthodromically elicited synaptic response consisted of an EPSC followed closely by an inhibitory postsynaptic current (IPSC). The IPSC portion of the elicited postsynaptic response was more sensitive to inhibition by hypoxia than was the EPSC. In some cells the EPSC exhibited a monophasic decline in amplitude during hypoxia. However, in a majority of cells, an initial decline in the amplitude of the EPSC was followed by a transient increase and subsequent depression.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				A. Ilie, D. Ciocan, A.-M. Zagrean, D. A. Nita, L. Zagrean, and M. Moldovan Endogenous Activation of Adenosine A1 Receptors Accelerates Ischemic Suppression of Spontaneous Electrocortical Activity J Neurophysiol, November 1, 2006; 96(5): 2809 - 2814. [Abstract] [Full Text] [PDF]

				Y. Zhang, P. Deng, Y. Li, and Z. C. Xu Enhancement of Excitatory Synaptic Transmission in Spiny Neurons After Transient Forebrain Ischemia J Neurophysiol, March 1, 2006; 95(3): 1537 - 1544. [Abstract] [Full Text] [PDF]

				H. S. Lukatch, C. E. Kiddoo, and M. B. MacIver Anesthetic-induced Burst Suppression EEG Activity Requires Glutamate-mediated Excitatory Synaptic Transmission Cereb Cortex, September 1, 2005; 15(9): 1322 - 1331. [Abstract] [Full Text] [PDF]

				N. J Allen and D. Attwell The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the juvenile rat hippocampus J. Physiol., December 1, 2004; 561(2): 485 - 498. [Abstract] [Full Text] [PDF]

				N. Matsumoto, E. Kumamoto, H. Furue, and M. Yoshimura GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat J Neurophysiol, January 1, 2003; 89(1): 257 - 264. [Abstract] [Full Text] [PDF]

				Z.-P. Pang, P. Deng, Y.-W. Ruan, and Z. C. Xu Depression of Fast Excitatory Synaptic Transmission in Large Aspiny Neurons of the Neostriatum after Transient Forebrain Ischemia J. Neurosci., December 15, 2002; 22(24): 10948 - 10957. [Abstract] [Full Text] [PDF]

				D. Centonze, E. Saulle, A. Pisani, G. Bernardi, and P. Calabresi Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia Brain, September 1, 2001; 124(9): 1855 - 1865. [Abstract] [Full Text] [PDF]

				I. A. Fleidervish, C. Gebhardt, N. Astman, M. J. Gutnick, and U. Heinemann Enhanced Spontaneous Transmitter Release Is the Earliest Consequence of Neocortical Hypoxia That Can Explain the Disruption of Normal Circuit Function J. Neurosci., July 1, 2001; 21(13): 4600 - 4608. [Abstract] [Full Text] [PDF]

				D. Jabaudon, M. Scanziani, B. H. Gahwiler, and U. Gerber Acute decrease in net glutamate uptake during energy deprivation PNAS, May 9, 2000; 97(10): 5610 - 5615. [Abstract] [Full Text] [PDF]

				G.-F. Tian and A. J. Baker Glycolysis Prevents Anoxia-Induced Synaptic Transmission Damage in Rat Hippocampal Slices J Neurophysiol, April 1, 2000; 83(4): 1830 - 1839. [Abstract] [Full Text] [PDF]

				A. Ouanonou, Y. Zhang, and L. Zhang Changes in the Calcium Dependence of Glutamate Transmission in the Hippocampal CA1 Region After Brief Hypoxia-Hypoglycemia J Neurophysiol, September 1, 1999; 82(3): 1147 - 1155. [Abstract] [Full Text] [PDF]

				E. Tanaka, S. Yamamoto, Y. Kudo, S. Mihara, and H. Higashi Mechanisms Underlying the Rapid Depolarization Produced by Deprivation of Oxygen and Glucose in Rat Hippocampal CA1 Neurons In Vitro J Neurophysiol, August 1, 1997; 78(2): 891 - 902. [Abstract] [Full Text] [PDF]

				J. Doherty and R. Dingledine Regulation of Excitatory Input to Inhibitory Interneurons of the Dentate Gyrus During Hypoxia J Neurophysiol, January 1, 1997; 77(1): 393 - 404. [Abstract] [Full Text] [PDF]