Objectives: 

Voltage-dependent K+ channels (Kv) control action potentials and membrane resting potential in nerve and muscle. In addition, Kv play a pivotal role in the leukocyte physiology. Numerous Kv blockers have demonstrated that Kv participate in the cell cycle progression. Leukocytes have a limited repertoire of Kv. Although Kv1.3 is major in T-lymphocytes, macrophages also express Kv1.5, which controls many physiological processes. Concerning B-lymphocytes, scarce information is available. The aim of the present work was to analyze the Kv isoforms expressed in B-cells and to characterize any putative physiological role.

Materials: 

We performed electrophysiological and pharmacological studies in B and T lymphocytes. In addition, we have generated a Kv1.5-deficient B lymphocyte cell line. Immunohistochemistry was also applied on human lymphoma samples.

Results: 

We report that, unlike Jurkat T cells, human Ramos and Raji B-lymphocytes express of both, Kv1.3 and Kv1.5 similarly to macrophages. Specific Kv-antagonists inhibited cell proliferation. In addition, by lentivirical infection of shKv1.5, which produced a knock-down of Kv1.5, we elucidate further the role of the channel in the B cell physiology by analyzing proliferation, migration and cell volume. Because Kv1.3 and Kv1.5 channels modulate proliferation and activation of different mammalian cells, these proteins have been analyzed by RT-PCR, immunoblotting and immunocytochemistry in a number of cell lines, lymphoid tissues, tumors and cancer cells from mouse and human samples. In most cancers, the expression patterns of Kv1.3 and Kv1.5 are remodeled. In addition, a correlation has been established between Kv1.5 abundance and grade of tumor malignancy (abundance of p53 and Ki67).

Conclusions: 

Because potassium channels may play a pivotal role in tumor cell proliferation, these proteins should be taken into account when designing new cancer treatment strategies.

Supported by BFU2011-23268 and CSD2008-00005 to AF (MINECO, Spain).