Differential Activity of Voltage- and Ca2+-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case

Abstract

Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+- or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3. Voltage dependence of activation and inactivation of Kv1.3 current were shifted up to by 15 mV to more negative potentials upon a prolonged incubation in the whole cell mode and displayed little difference at a stable state in all cell lines but CEM, where the activation curve was biphasic, with a high and low potential components. In Jurkat, KCa currents were dominated by apamine-sensitive KCa2.2 channels, whereas only KCa3.1 current was detected in healthy T and leukemic CEM and MOLT-3 cells. Despite a high proliferation potential of Jurkat cells, Kv and KCa currents were unexpectedly small, more than 10-fold lesser as compared to activated healthy human T cells, CEM and MOLT-3, which displayed characteristic Kv1.3high:KCa3.1high phenotype. Our results suggest that Jurkat cells represent perhaps a singular case and call for more extensive studies on primary leukemic T cell lines as well as a verification of the therapeutic potential of specific KCa3.1 blockers to combat acute lymphoblastic T leukemias.

Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of Kv1.3 potassium channels, AKT and ERK1/2 signaling

“…To exclude the possibility of a Jurkat cell-specific effect, we analysed AraC-induced cell death of the human acute lymphoblastic leukemia cell line CEM. As in Jurkat cells, K v current in CEM cells is exclusively mediated by K v 1.3 channels [50]. Again, AraC/memantine co-treatment enhanced cell death of CEM cells compared to cells treated with AraC alone (Fig.…”

“…Using murine lymphocytes, we previously reported that memantine blocks K v 1.3 and K Ca 3.1 channels [37]. Therefore, we do not exclude a possibility of memantine affecting K Ca 3.1 channels (and maybe other ion channels) [50, 54, 56, 57] which might contribute to memantine’s potentiation of AraC cytotoxicity. Compared to memantine treatment alone, knockdown of K v 1.3 mRNA in Jurkat cells was more effective in inducing cell death.…”

Immunosuppressive effects of a novel potassium channel toxin Ktx-Sp2 from Scorpiops Pocoki

“…Two major types of K + channels are expressed by the human Jurkat T cells: Kv1.3 [8], and the small conductance Ca 2+ -dependent K + channel (SKCa2) which is activated by a cytosolic Ca 2+ rise [9]. We then examined whether Ktx-Sp2 could also regulate the activation of endogenous Kv1.3 expressed by human Jurkat T cells which is commonly used to study T cell signaling [10].…”

Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol

“…Voltage-dependent K + channels in B and T cells are functionally represented by the single member, Kv1.3 ( 181 , 182 ). The Kv1.3 current is robustly presented in T-ALL, albeit it is lacking in B-ALL ( 183 , 184 ). The surface expression of Kv1.3 channels is downregulated by Nedd4-2 and upregulated by different SGK isoforms ( 185 ).…”