Journal of Neurophysiology, Vol 56, Issue 2 424-438, Copyright © 1986 by APS

ARTICLES

Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. II. Role of extracellular potassium

Y. Yaari, A. Konnerth and U. Heinemann

The role of extracellular K+ (K+o) in nonsynaptic epileptogenesis induced in the CA1 area of rat hippocampal slices by lowering [Ca2]o was studied with K+-selective microelectrodes (KSMs). Extracellular field potentials and [K+]o were recorded simultaneously with 1-2 KSMs in the CA1 stratum pyramidale. In slices perfused with an oxygenated standard physiological solution (containing 2 mM Ca2+), base-line [K+]o was stable for several hours. The washout of Ca2+o was accompanied by a gradual tonic rise of [K+]o. Spontaneous and stimulus-evoked maximal seizurelike events (SLEs) appeared when [K+]o was approximately 0.5 mM above the initial 5 mM base line. These changes were reversible in normal medium. When K+o was pressure ejected in the CA1 stratum pyramidale of spontaneously active slices, a local rise in [K+]o of approximately 0.5 mM was necessary to trigger a SLE. A similar apparent [K+]o "threshold" was associated with SLEs evoked by electrical stimulation. Increasing [K+] in the perfusing solution by small increments (1 mM) markedly enhanced SLEs frequency and velocity of spread and decreased the period of absolute refractoriness that succeeded each paroxysm. Similar changes occurred during periods of transient hypoxia. Small [K+] decreases in the perfusate had the converse effects. Spontaneous SLEs were associated with phasic increases in [K+]o. In simultaneous [K+]o recordings from two layers, these transients were largest (up to 3.5 mM above base line) and rose more steeply at the stratum pyramidale. Toward the outer dendritic layers they became smaller, slower in time course, and delayed in onset. We conclude that the main source for these [K+]o transients are the hippocampal pyramidal cell bodies, which discharge intensely during a SLE, and that excess K+o is spatially dispersed around the discharge zone of the paroxysm. [K+]o continued to rise, though at a slower rate, throughout the course of a SLE. Following SLE termination, [K+]o decayed slowly to base line. The invasion of a CA1 region by a propagating SLE was preceded quite often by a slow rise in [K+]o. A sudden transition to a steeply rising [K+]o marked the explosive recruitment of this region into the discharge zone of the spreading paroxysm. The total (tonic and phasic) increase in [K+]o during SLEs did not surpass a maximal level of approximately 9 mM, which was the ceiling level of [K+]o in low [Ca2+]o. However, when spreading depression occurred, [K+]o rose up to 30-40 mM for several minutes. Spreading depression rarely appeared spontaneously despite the recurrence of SLEs, but could be provoked by repetitive electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				D. S. Shin and P. L. Carlen Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+ J Neurophysiol, May 1, 2008; 99(5): 2203 - 2219. [Abstract] [Full Text] [PDF]

				Z. Feng and D. M. Durand Decrease in Synaptic Transmission Can Reverse the Propagation Direction of Epileptiform Activity in Hippocampus In Vivo J Neurophysiol, March 1, 2005; 93(3): 1158 - 1164. [Abstract] [Full Text] [PDF]

				Z. Feng and D. M. Durand Low-Calcium Epileptiform Activity in the Hippocampus In Vivo J Neurophysiol, October 1, 2003; 90(4): 2253 - 2260. [Abstract] [Full Text] [PDF]

				J. Shuai, M. Bikson, P. J. Hahn, J. Lian, and D. M. Durand Ionic Mechanisms Underlying Spontaneous CA1 Neuronal Firing in Ca2+-Free Solution Biophys. J., March 1, 2003; 84(3): 2099 - 2111. [Abstract] [Full Text] [PDF]

				R. D'Ambrosio, D. S. Gordon, and H. R. Winn Differential Role of KIR Channel and Na+/K+-Pump in the Regulation of Extracellular K+ in Rat Hippocampus J Neurophysiol, January 1, 2002; 87(1): 87 - 102. [Abstract] [Full Text] [PDF]

				R. S. Ghai, M. Bikson, and D. M. Durand Effects of Applied Electric Fields on Low-Calcium Epileptiform Activity in the CA1 Region of Rat Hippocampal Slices J Neurophysiol, July 1, 2000; 84(1): 274 - 280. [Abstract] [Full Text] [PDF]

				G. Menna, C. K. Tong, and M. Chesler Extracellular pH Changes and Accompanying Cation Shifts During Ouabain-Induced Spreading Depression J Neurophysiol, March 1, 2000; 83(3): 1338 - 1345. [Abstract] [Full Text] [PDF]

				Z.-Q. Xiong, P. Saggau, and J. L. Stringer Activity-Dependent Intracellular Acidification Correlates with the Duration of Seizure Activity J. Neurosci., February 15, 2000; 20(4): 1290 - 1296. [Abstract] [Full Text] [PDF]

				R. Demir, L. B. Haberly, and M. B. Jackson Sustained Plateau Activity Precedes and Can Generate Ictal-Like Discharges in Low-Cl- Medium in Slices from Rat Piriform Cortex J. Neurosci., December 15, 1999; 19(24): 10738 - 10746. [Abstract] [Full Text] [PDF]

				R. E. Westenbroek, S. B. Bausch, R. C. S. Lin, J. E. Franck, J. L. Noebels, and W. A. Catterall Upregulation of L-Type Ca2+ Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia J. Neurosci., April 1, 1998; 18(7): 2321 - 2334. [Abstract] [Full Text] [PDF]

				E. Pan and J. L. Stringer Role of Potassium and Calcium in the Generation of Cellular Bursts in the Dentate Gyrus J Neurophysiol, May 1, 1997; 77(5): 2293 - 2299. [Abstract] [Full Text] [PDF]

				M. S. Jensen and Y. Yaari Role of Intrinsic Burst Firing, Potassium Accumulation, and Electrical Coupling in the Elevated Potassium Model of Hippocampal Epilepsy J Neurophysiol, March 1, 1997; 77(3): 1224 - 1233. [Abstract] [Full Text] [PDF]

				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]

				M. Dichter and G. Ayala Cellular mechanisms of epilepsy: a status report Science, July 10, 1987; 237(4811): 157 - 164. [Abstract] [PDF]