Thioredoxin increases neuronal delayed rectifier K+ current

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[Objective] Thioredoxin (Trx), which exhibits thiol-protein oxidoreductase (TPOR) activity via a Cys-Gly-Pro-Cys motif, is expressed in high levels in some brain regions that are involved in cardiovascular control. In previous studies, we demonstrated that macrophage migration inhibitory factor (MIF) blunts the stimulatory actions of angiotensin II (Ang II) on sympathetic outflow and cardiovascular function by inhibiting neuronal delayed rectifier K+ current (Ikv). Further, we demonstrated that these neuronal actions of MIF are mediated by it's TPOR activity and scavenging of superoxides. In this study, we speculated that Trx can inhibit Ikv and serve as a negative regulator of Ang II, similar to MIF. [Methods] Neuronal co-cultures were prepared from the brainstem and a hypothalamic block of newborn Sprague Dawley rats. Using patch-clamp techniques, we recorded neuronal Ikv during 100 msec voltage steps from a holding potential of −40 to +10 mV. Trx was applied intracellularly to the neurons and the time course of changes in Ikv was observed. [Results] Intracellular application of Trx (8 nM) started to increase the Ikv within 5–10 minutes, and exhibited a maximal effect after 15–20 minutes. The average change in current density (pA/pF) was from 31.70 ± 0.56 (M±SE) to 43.71 ± 2.89 (n=8), a significant value (p<0.01). Pretreatment with the cell permeable superoxide scavenger Tiron (1 mM), inhibited the effect of Trx on Ikv. [Conclusion] We have made the novel observation that Trx increases Ikv, and this action involves TPOR activity and the scavenging of superoxides. This mechanism is similar to that exhibited by MIF, and we hypothesize that Trx also may act as a negative regulator of Ang II actions in neurons.