Characteristics of Store-Operated Ca ²⁺ -Permeable Current in Monocytic U937 Cells

The electrophysiological properties of store-operated Ca ²⁺ -permeable current in monocytic U937 cell line were characterized. The whole-cell voltage clamp technique with patch pipette containing Cs-internal solution was carried out. Membrane currents were elicited by the ramp pulses from -90 mV to +40 mV with a duration of 200 msec. After the presence of Ca ²⁺ -free Tyrode's solution plus cyclopiazonic acid (30 μM), A23187 (10 μM) or ATP (30 μM) in cells for 10 minutes, a significant inward current was markedly elicited by further application of CaCl ₂ (2 mM). This net inward current was reversed at about -12 mV with inward rectification. The reversal potential of this current was not significantly altered by the replacement of intracellular Cl ^- concentrations. The activation of this current is thus referred to as be store-operated Ca ²⁺ -permeable current (I _SOC ). The addition of LaCl ₃ (100 μM) or NiCl ₂ (100 μM) markedly blocked I _SOC . The replacement of NaCl with N-methyl-D-glucamine chloride decreased the amplitude of this current at the level of -80 mV by 50%. Nifedipine (3-100 μM) effectively suppressed the amplitude of I _SOC in a concentration-dependent manner. The EC ₅₀ value for nifedipine-induced inhibition of I _SOC is 10 μM. However, verapamil (30 μM) or Bay K 8644 (30 μM) did not produce any effect on it. The present studies indicate that in monocytic U937 cells, Ca ²⁺ entry elicited by store depletion is mediated through store-operated Ca ²⁺ -permeable channel which is responsive to nifedipine.