Abstract

The effects of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on inward rectifier potassium [K(IR)] currents and on cell morphology have been studied in cultured human oligodendrocytes. Cell-attached patches were used to isolate and record unitary currents through an inward rectifier K+ channel with a conductance of 23 pS. In control oligodendrocytes the mean open times showed an exponential dependence on patch potential with an e-fold decrease over a patch hyperpolarization of 28 mV. Treatment of oligodendrocytes with rhTNF (at 250 ng/ml for 24-48 h) had significant actions to diminish the mean open times of K(IR) relative to control values. At cell resting potential the mean open times were reduced by 60% after rhTNF application; the amplitudes of unitary currents or the extrapolated zero-current potentials were not significantly changed by the cytokine. The rhTNF treatments were not cytotoxic to cultured human oligodendrocytes; however, in some experiments rhTNF caused evident retraction of cell processes.

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