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dc.contributor.authorVera-Zambrano, Albaes_ES
dc.contributor.authorCruz, Alicia de laes_ES
dc.contributor.authorPeraza, Diego A.es_ES
dc.contributor.authorZapata, Juan M.es_ES
dc.contributor.authorValenzuela, Carmenes_ES
dc.contributor.authorPérez-Chacón, Gemaes_ES
dc.contributor.authorGonzález, Teresaes_ES
dc.identifier.citationVI RECI Meeting (2017)es_ES
dc.descriptionResumen del póster presentado al VI Meeting de la Red Española de Canales Ióniocs (RECI), celebrado en Santiago de Compostela del 6 al 8 de septiembre de 2017.es_ES
dc.description.abstractFludarabine (F-ara-A) is a purine analogue commonly used in the treatment of indolent B cell malignancies that interferes with different aspects of DNA and RNA synthesis. KV1.3 potassium channels are membrane proteins involved in the control of K+ homeostasis and in the maintenance of the resting potential of the cell, thus controlling signaling events, proliferation and apoptosis in lymphocytes. The aim of this study was to determine if F-ara-A modulates KV currents in human B lymphocytes. We show that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1.3 levels were higher in BL2 compared to those in Dana cells. However, KV currents in the plasma membrane were similar in both cell lines. These KV currents were abrogated by the specific KV1.3 channel inhibitor PAP-1, indicating that most KV currents in these B cell lines are controlled by KV1.3. F-ara-A, at a concentration (3.5 µM) similar to that achieved in the plasma of fludarabine phosphate-treated patients (3 µM), inhibited KV1.3 currents by 61±6.3% and 52.3±6.3% in BL2 and Dana B cells, respectively. The inhibitory effect of F-ara-A was concentration dependent and showed an IC50 value of 0.36±0.04 µM and a nH value of 1.07±0.15 in BL2 cells and 0.34±0.13 µM (IC50) and 0.77±0.11 (nH) in Dana cells. This inhibitory effect of F-ara-A on the activity of plasma membrane KV1.3 was observed in these cells irrespective of their cytotoxic effect. F-ara-A had no effect on heterologously expressed KV1.3 channels, suggesting an indirect mechanism of inhibition. Fludarabine (F-ara-A), a chemotherapeutic drug extensively used in clinics, strongly inhibits KV1.3 currents in B lymphoma and lymphoblastoid cells. Although this inhibitory activity is not sufficient to induce cell death, it might still contribute to the cytotoxic effect of the drug.es_ES
dc.titleFludarabine inhibits KV1.3 currents in human B lymphocyteses_ES
dc.typepóster de congresoes_ES
dc.description.peerreviewedPeer reviewedes_ES
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