Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner

Figure 4

IR stimulates Ca²⁺ entry through TRPM2 channels especially in Bcl-2-overexpressing Jurkat cells. (a) Whole-cell current tracings recorded in Jurkat-Bcl-2 cells irradiated with 0 Gy (1st and 2nd tracings) or 5 Gy (3rd and 4th tracings, 2 h after IR). Records were obtained in unpaired experiments as described in Figure 1(a) before (1st and 3rd tracings) and during bath application of the TRPM2 inhibitor ACA (20 μM, 2nd and 4th tracings). (b) Relationship of the mean (± SE, ) current density and the voltage recorded as in (a) in Jurkat-Bcl-2 cells irradiated with 0 Gy (open circles) or 5 Gy (closed triangles). (c) Mean (± SE, ) conductance density of control (0 Gy, open bars) and irradiated (5 Gy, 2–5 h after IR) Jurkat-vector (left) and Jurkat-Bcl-2 cells (right) recorded as in (a) in the absence or presence of ACA. Conductance densities were calculated for the outward currents as shown by the blue and red line in (b) for control and irradiated cells, respectively. (d, e) Mean (± SE, ) fura-2 340/380 nm ratio (d) and delta fura-2 ratio (e) as measures of cytosolic free Ca²⁺ concentration and Ca²⁺ entry in Ca²⁺-depleted cells, respectively. Ca²⁺-specific fura-2 fluorescence was recorded by imaging in control (0 Gy, open circles and bars) and irradiated (5 Gy, closed triangles and bars, 1.5–5 h after IR) Jurkat-vector and Jurkat-Bcl-2 cells using extracellular Ca²⁺ removal/readdition protocol. Ca²⁺ readdition was performed in the absence (vehicle) or presence of ACA (20 μM). indicates , ANOVA.

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