Journal of Neurophysiology, Vol 63, Issue 3 385-394, Copyright © 1990 by APS

ARTICLES

Different responses of CA1 and CA3 regions to hypoxia in rat hippocampal slice

K. Kawasaki, S. F. Traynelis and R. Dingledine
Department of Pharmacology, University of North Carolina, Chapel Hill 27599.

1. To study the effects of brief periods of hypoxia on cellular functions in the rat hippocampal slice, extracellular and intracellular recordings were made from pyramidal neurons, and interstitial potassium activity ([K+]o) was measured in the pyramidal cell layers. Slices were perfused in an interface chamber at 36-37 degrees C with medium containing 8.5 mM [K+]o. Hypoxia was induced by switching the overflow gas from O2-CO2 to N2-CO2. 2. Brief periods of hypoxia (5-60 s) produced electrographic seizures with typical tonic and clonic components in 53% of 293 slices that generated spontaneous interictal bursts. Hypoxia-induced seizures were usually initiated in and restricted to the Ca1 region; only 2.5% of these slices generated seizures in CA3. In contrast to the CA1 region, the CA3 region could undergo spreading depression during hypoxia. The probability of seizure generation in CA1 was increased with increasing duration of hypoxia and was greatly reduced by lowering the bath temperature a few degrees. 3. [K+]o gradually increased in the CA1 and CA3 cell layers during the 20 s leading up to an hypoxia-induced seizure. [K+]o rose to approximately 9.8 mM (from a base line of 8.5 mM) in CA1 just before a seizure and to 11.4 mM during the seizure. After hypoxia, [K+]o reached a higher level in CA1 than in CA3, regardless of whether 1 microM tetrodotoxin was present to eliminate differences in cell firing in the two regions. CA1 pyramidal cells and glia gradually depolarized by several millivolts during and after hypoxia; no initial hyperpolarizing phase was detected. 4. Burst input from CA3 was necessary for hypoxia-induced seizures. The frequency and intensity of spontaneous burst-firing in CA3 remained steady in the period leading up to a CA1 seizure episode. In contrast, the intensity of synaptically driven bursts in CA1 grew markedly just before seizure onset. N-methyl-D-aspartate (NMDA) receptors participated in the crescendo of increasingly synchronous activity in CA1, because the competitive NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV, 30 microM), stereoselectively reduced seizure intensity. 5. Hypoxia-induced seizures were followed by a depressant phase, which was manifested most prominently by a prolonged (up to several minutes) reduction in the frequency and intensity of burst-firing in the CA3 region, hyperpolarization of CA1 neurons, and undershoot of [K+]o. In normal (3.5 mM) [K+]o, synaptically driven population spikes in CA1 were only reduced in amplitude by hypoxia; hypoxia did not induce seizures in 3.5 mM [K+]o.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				H. Misonou, D. P. Mohapatra, M. Menegola, and J. S. Trimmer Calcium- and Metabolic State-Dependent Modulation of the Voltage-Dependent Kv2.1 Channel Regulates Neuronal Excitability in Response to Ischemia J. Neurosci., November 30, 2005; 25(48): 11184 - 11193. [Abstract] [Full Text] [PDF]

				E. Tanaka, H. Uchikado, S. Niiyama, K. Uematsu, and H. Higashi Extrusion of Intracellular Calcium Ion After In Vitro Ischemia in the Rat Hippocampal CA1 Region J Neurophysiol, August 1, 2002; 88(2): 879 - 887. [Abstract] [Full Text] [PDF]

				D. Gozal, J. M. Daniel, and G. P. Dohanich Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat J. Neurosci., April 1, 2001; 21(7): 2442 - 2450. [Abstract] [Full Text] [PDF]

				S. Bahar, D. Fayuk, G. G. Somjen, P. G. Aitken, and D. A. Turner Mitochondrial and Intrinsic Optical Signals Imaged During Hypoxia and Spreading Depression in Rat Hippocampal Slices J Neurophysiol, July 1, 2000; 84(1): 311 - 324. [Abstract] [Full Text] [PDF]

				N. R. Kreisman, S. Soliman, and D. Gozal Regional Differences in Hypoxic Depolarization and Swelling in Hippocampal Slices J Neurophysiol, February 1, 2000; 83(2): 1031 - 1038. [Abstract] [Full Text] [PDF]

				M. Tanabe, M. Mori, B. H. Gahwiler, and U. Gerber Apamin-Sensitive Conductance Mediates the K+ Current Response During Chemical Ischemia in CA3 Pyramidal Cells J Neurophysiol, December 1, 1999; 82(6): 2876 - 2882. [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]

				Z. B. Yao, X. Li, Z. C. Xu, and J. T. Povlishock GABAergic and Asymmetrical Synapses on Somata of GABAergic Neurons in CA1 and CA3 Regions of Rat Hippocampus: A Quantitative Electron Microscopic Analysis Stroke, August 1, 1996; 27(8): 1411 - 1416. [Abstract] [Full Text]

				T Nitta, J. Oksenberg, N. Rao, and L Steinman Predominant expression of T cell receptor V alpha 7 in tumor-infiltrating lymphocytes of uveal melanoma Science, August 10, 1990; 249(4969): 672 - 674. [Abstract] [PDF]

				C. McBain, S. Traynelis, and R Dingledine Regional variation of extracellular space in the hippocampus Science, August 10, 1990; 249(4969): 674 - 677. [Abstract] [PDF]