Biophysical Characterization of the Potassium Channel Kv1.3 in B Cells from Patients Affected by Chronic Lymphocytic Leukemia

Abstract

Recent discoveries identified ion channels as possible targets for cancer treatment. We have previously demonstrated that inhibition of the mitochondria-located potassium channel Kv1.3 (mtKv1.3) by membrane permeant inhibitors Psora-4, PAP-1 and clofazimine triggers cell death both in vitro and in vivo, resulting in reduction of tumor volume up to 90% (Leanza et al, 2012, EMBO Molecular Medicine). Importantly, these compounds are able to selectively kill pathological B cells from patients affected by chronic lymphocytic leukemia (B-CLL) (Leanza et al, 2013, Leukemia). Here, we determined the expression profile of Kv1.3 by western blot comparing B cells from healthy subjects and B-CLL patients in whole cell lysates as well as in purified mitochondria. An increased expression of the channel in pathological cells compared to normal ones was observed. To our knowledge, electrophysiological characterization of Kv1.3 in B-CLL cells has not been performed up to now. By measuring Kv1.3 current in patch clamp experiments, both at whole cell and at single channel levels, here we show that increased protein expression was correlated with enhanced channel activity. Biophysical and pharmacological properties of Kv1.3 from the two cells types are reported. Experiments with pathological B-cells cultured in the presence of cells mimicking bone marrow environment are in progress.