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This Article Full Text Full Text (PDF) All Versions of this Article: 93/2/843    most recent 01224.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Hadjilambreva, G. Articles by Strauss, U. Search for Related Content PubMed PubMed Citation Articles by Hadjilambreva, G. Articles by Strauss, U.

Neuromodulation by a Cytokine: Interferon- Differentially Augments Neocortical Neuronal Activity and Excitability

Department of Neurology, Neurobiological Laboratory, University of Rostock, Germany

Submitted 17 December 2003; accepted in final form 22 September 2004

The immunomodulatory cytokine interferon- (IFN-) is used in the treatment of autoimmune diseases such as multiple sclerosis. However, the effect of IFN- on neuronal functions is currently unknown. Intracellular recordings were conducted on somatosensory neurons of neocortical layers 2/3 and 5 exposed to IFN-. The excitability of neurons was increased by IFN- (10–10,000 U/ml) in two kinetically distinct, putatively independent manners. First IFN- reversibly influenced the subthreshold membrane response by raising the membrane resistance R_M 2.5-fold and the membrane time constant 1.7-fold dose-dependently. The effect required permanent exposure to IFN- and was reduced in magnitude if the extracellular K⁺ was lowered. However, the membrane response to IFN- in the subthreshold range was prevented by ZD7288 (a specific blocker of I_h) but not by Ni²⁺, carbachol, or bicuculline, pointing to a dependence on an intact I_h. Second, IFN- enhanced the rate of action potential firing. This effect was observed to develop for >1 h when the cell was exposed to IFN- for 5 min or >5 min and showed no reversibility (210 min). Current-discharge (F-I) curves revealed a shift (prevented by bicuculline) as well as an increase in slope (prevented by carbachol and Ni²⁺). Layer specificity was not observed with any of the described effects. In conclusion, IFN- influences the neuronal excitability in neocortical pyramidal neurons in vitro, especially under conditions of slightly increased extracellular K⁺. Our blocker experiments indicate that changes in various ionic conductances with different voltage dependencies cause different IFN- influences on sub- and suprathreshold behavior, suggesting a more general intracellular process induced by IFN-.

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