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

Abstract

Previous reports have suggested that receptors for immunoglobulin G (IgG), FcγRs, directly activate a non-selective 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, 500-507). To investigate the mechanisms underlying membrane conductance changes following human high affinity (FcγRI) receptor activation, we have used the human monocytic cell line U937 and combined conventional whole cell patch-clamp recordings with single cell furs-2 Ca2+ measurements. Using a K+-free internal solution, antibody cross-linking of IgG-occupied FcγRI 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 picasiemens and a mean opening time of 4.5 ms. This current was also activated by rises in intracellular Ca2+ induced by ionomycin (3 μM) or thapsigargin (1 μM). 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, FcγRI, or the low affinity receptor, FcγRII. These results demonstrate that FcγRI activation triggers a novel Ca2+-activated channel selective for monovalent cations and that neither FcγRI nor FcγRII can directly activate a channel.