Fcgamma 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), FcgammaRs, 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, 500-507). To investigate the mechanisms underlying membrane conductance changes following human high affinity (FcgammaRI) 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 FcgammaRI 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 microM) or thapsigargin (1 microM). 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, FcgammaRI, or the low affinity receptor, FcgammaRII. These results demonstrate that FcgammaRI activation triggers a novel Ca2+-activated channel selective for monovalent cations and that neither FcgammaRI nor FcgammaRII can directly activate a channel.
Floto
R A
RA
Physiological Laboratory, Downing Street, Cambridge CB2 3EG, United Kingdom.
Somasundaram
B
B
Allen
J M
JM
Mahaut-Smith
M P
MP
D002118:Calcium / Q000378:metabolism*; D002412:Cations / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D017136:Ion Transport; D009000:Monocytes / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction
D002412:Cations; D011961:Receptors, Fc; D002118:Calcium