Bacterial endotoxins impair electrophysiological properties of cultured astrocytes but not of cultured neurons.
The endotoxins of bacteria are lipopolysaccharides which are released in the central nervous system during bacterial meningitis. Endotoxin titers in cerebrospinal fluid correspond to the appearance of severe neurological symptoms like seizures and coma. The pathogenic mechanism, however, by which endotoxins disturb neuronal function, is unclear. The functional deficit may originate either from direct alteration of neuronal excitability or from indirect effects mediated by glial cells. Therefore, we investigated the effects of lipopolysaccharides on electrophysiological properties of cortical neurons and astrocytes in separate cell cultures. Membrane potential, resistance and membrane currents of neurons were unaffected. By contrast, astrocytes depolarized markedly in a dose dependent manner (concentration range 1.0-10.0 micrograms/ml). The depolarization was Na+ dependent and amiloride sensitive (250 microM), both indicating an activation of an electrogenic sodium dependent transport system like the Na+/Ca2+ exchanger as a source of the depolarization. These results suggest that endotoxin induced neurological deficits are not caused by direct effects on neurons, but may result from an impaired glial cell function.
Department of Neurology, Heinrich-Heine-University, Dusseldorf, Germany.
H
H
Köller
J
J
Buchholz
M
M
Siebler
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004594:Electrophysiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology
D008070:Lipopolysaccharides; D000584:Amiloride; D003513:Cycloheximide; D012964:Sodium