Role of Glial Cells in Seizures and Epilepsy: Intracellular Calcium Oscillations sn Spatial Buffering.

Abstract

Spatial Buffering During Slow and Paroxysmal Sleep Oscillations in Cortical Networks of Glial Cells In Vivo Amzica F, Massimini M, Manfridi A J Neurosci 2002;22:1042–1053 The ability of neuroglia to buffer local increases of extracellular K+ has been known from in vitro studies. This property may confer on these cells an active role in the modulation and spreading of cortical oscillatory activities. We addressed the question of the spatial buffering in vivo by performing single and double intraglial recordings, together with measures of the extracellular K+ and Ca2+ concentrations ([K+]out and [Ca2+]out) in the cerebral cortex of cats under ketamine and xylazine anesthesia during patterns of slow sleep oscillations and spike-wave seizures. In addition, we estimated the fluctuations of intraglial K+ concentrations ([K+]in). Measurements obtained during the slow oscillation indicated that glial cells phasically take up part of the extracellular K+ extruded by neurons during the depolarizing phase of the slow oscillation. During this condition, the redistribution of K+ appeared to be local. Large steady increases of [K+]out and phasic potassium accumulations were measured during spike-wave seizures. In this condition, [K+]in rose before [K+]out if the glial cells were located at some distance from the epileptic focus, suggesting faster K+ diffusion through the interglial syncytium. The simultaneously recorded [Ca2+]out dropped steadily during the seizures to levels incompatible with efficient synaptic transmission, but also displayed periodic oscillations, in phase with the intraseizure spike-wave complexes. In view of this fact, and considering the capability of K+ to modulate neuronal excitability both at the presynaptic and postsynaptic levels, we suggest that the K+ long-range spatial buffering operated by glia is a parallel synchronizing and/or spreading mechanism during paroxysmal oscillations. Calcium Oscillations in Neocortical Astrocytes under Epileptiform Conditions Tashiro A, Goldberg J, Yuste R J Neurobiol 2002;50:45–55 Morphological and functional alterations in astrocytic glia are often found in epileptic syndromes, although the exact role of astrocytes in epilepsy is poorly understood. During calcium imaging of epileptiform events in juvenile neocortical slices we previously discovered cells with spontaneous oscillations in their intracellular free calcium concentration ([Ca(2+)](i)). We have now characterized these oscillations using two in vitro models of epilepsy and find that they are produced by astrocytes. Astrocytic oscillations are widespread throughout the imaged territories, are remarkably regular and have long periods, averaging 100 s, which become shorter during development. Astrocytic oscillations are uncorrelated among themselves and with epileptiform events, are blocked by internal release antagonists and are stimulated by caffeine. Astrocytic calcium oscillations could mediate reactive astrogliosis, contribute to the pathogenesis of chronic epileptic syndromes, and be used as a diagnostic test for epileptic tissue.