Tumour necrosis factor-alpha increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells.
Tumour necrosis factor (TNF)-alpha, a strong immune mediator, is released within the brain during inflammatory diseases and contributes to immunological activation of glial cells. Here we report that, in astrocytes, TNF-alpha also affects the intracellular Ca2+ homeostasis and basic electrophysiological properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in a cell culture model, we found that TNF-alpha (10-1000 U ml-1), but not interleukin 1 or 6, induced a slow but more than two-fold increase of the intracellular Ca2+ concentration, which could be blocked by Co2+ (1.0 mM), verapamil (100 microM) or omission of external Ca2+. This intracellular Ca2+ increase was accompanied by a marked decrease of the membrane potential by 35 mV. CSF of patients with bacterial meningitis, known to contain large amounts of TNF-alpha, induced a similar depolarization of astrocytes, which was markedly reduced by a neutralizing anti-TNF-alpha antibody. We conclude that TNF-alpha induces an increase of intracellular Ca2+ and a depolarization in astrocytes with the consequence of disturbing voltage-dependent glial functions such as regulation of local ion concentrations and glutamate uptake. During inflammatory CNS diseases this immuno-electrical coupling may contribute to an impairment of neuronal function.
Köller
H
H
Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany.
Thiem
K
K
Siebler
M
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D002118:Calcium