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 microM), A23187 (10 microM) or ATP (30 microM) in cells for 10 minutes, a significant inward current was markedly elicited by further application of CaCl2 (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 (ISOC). The addition of LaCl3 (100 microM) or NiCl2 (100 microM) markedly blocked ISOC. 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 microM) effectively suppressed the amplitude of ISOC in a concentration-dependent manner. The EC50 value for nifedipine-induced inhibition of ISOC is 10 microM. However, verapamil (30 microM) or Bay K 8644 (30 microM) did not produce any effect on it. The present studies indicate that in monocytic U937 cells, Ca2+ entry elicited by store depletion is mediated through store-operated Ca(2+)-permeable channel which is responsive to nifedipine.