Neuron-glia relationships in human and experimental epilepsy: a biochemical point of view.
The generation of focal cortical epilepsy as observed in human partial complex seizures is presumably due to enhanced physiologic responses or paroxysmal depolarization shifts (PDSs). However, the molecular mechanism that underlies these phenomena remains unknown. It could be due to a genetically determined error in a structural or regulatory protein or to posttranslational events that modulate membrane excitability. Since neither neuronal PDSs or interictal EEG spikes are sufficient to produce clinical epilepsy, the clinical expression of epilepsy may need the breakdown of neuronal or glial mechanisms that limit the spread of seizures. Hence, biochemical membrane studies of neurons and glia are necessary to understand the expression of human and experimental epilepsy. This chapter will review the role of glia in controlling neuronal excitability and neuron-glia relationships in experimental and human epilepsy. Data exploring the hypothesis that glial control of extracellular K+ or (K+)o is deficient in focal epilepsy induced by cold lesions will be reviewed. The role of glial carbonic anhydrase (CA) and glial control of putative amino acid transmitters in audiogenic epilepsy will be discussed. In the cold lesion, (K+)o activation constants of synaptosomal (Na+,K+)-ATPase are significantly decreased in the actively firing chronic focus, suggesting that the apparent affinity of the synaptosomal enzyme for K+ was increased within epileptic tissue that was actively firing. Interestingly, while sustained focal paroxysms could raise synaptosomal (Na+,K+)-ATPase, glial (Na+,K+)-ATPase and its activation by (K+)o remained decreased during sustained paroxysms in both acute and chronic lesions. Moreover, while the decrease of the absolute level of glial enzyme activity was less evident 45 days after lesion production, the poor response of glial enzyme to (K+)o never reversed to "normal" values. Hence, these experiments provided new information that glial (Na+,K+)-ATPase responds to K+ in a different manner when compared to synaptic enzyme. Glial ATPase and its activation by (K+)o remain decreased in either actively discharging acute lesions or in the indolent chronic foci. This could mean a reduction in the ability of glial membranes to maintain (K+)o homeostasis. As already suggested by Dichter, the impairment in glial control of elevated (K+)o could be mainly responsible for the transition of interictal discharges to ictal episodes, within the primary and the secondary foci.(ABSTRACT TRUNCATED AT 400 WORDS)
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D000596:Amino Acids / Q000502:physiology; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000201:enzymology; D002256:Carbonic Anhydrases / Q000378:metabolism; D004827:Epilepsy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007477:Ions; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D007477:Ions; D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002256:Carbonic Anhydrases; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium