Fc gamma receptor I activation triggers a novel Ca2+-activated current selective for monovalent cations in the human monocytic cell line, U937

Previous reports have suggested that receptors for immunoglobulin G (IgG), Fc gamma Rs, directly activate a nonselective cation channel (Young, J. D.-E., Unkeless, J. C., Young, T. M., Mauro, A., and Cohn, Z. A. (1983) Nature 306, 186-189; Nelson, D. J., Jacobs, E. R., Tang, J. M., Zeller, J. M., and Bone, R. C. (1985) J. Clin. Invest. 76, 500607). To investigate the mechanisms underlying membrane conductance changes following human high affinity (Fc gamma RI) receptor activation, we have used the human monocytic cell line U937 and combined conventional whole cell patch-clamp recordings with single cell fura-2 Ca2+ measurements. Using a K+-free internal solution, antibody cross-linking of IgG-occupied Fc gamma RI activated an inward current at negative potentials, whose amplitude and time course mirrored the concomitant rise in intracellular Ca2+. Current-voltage relationships, obtained under different ionic conditions, revealed a monovalent cation-selective conductance that, under physiological conditions, would result in Na+ influx. Noise analysis of current recordings indicated a single channel conductance of 18 picosiemens and a mean opening time of 4.5 ms. This current was also activated by rises in intracellular Ca2+ induced by ionomycin (3 mu M) or thapsigargin (1 mu M). Addition of the Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid to the intracellular medium abolished any channel activation by ionomycin, Fc gamma RI, or the low affinity receptor, Fc gamma RII. These results demonstrate that Fc gamma RI activation triggers a novel Ca2+-activated channel selective for monovalent cations and that neither Fc gamma RI nor Fc gamma RII can directly activate a channel.