Initial characterization of the calcium channel activated by the cross-linking of the receptors for immunoglobulin E.
It is currently thought that aggregation of the receptor for immunoglobulin E on mast cells, basophils, and a tumor analog, rat basophilic leukemia (RBL) cells, induces an enhanced permeability of the plasma membrane to calcium, thereby initiating degranulation of the cells. Even in the absence of calcium ions, aggregation of the receptor causes depolarization of the plasma membrane (Kanner, B. I., and Metzger, H. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 5744-5748), suggesting that other ions can traverse the putative channel. Direct evidence for this now has been obtained with measurements of increased 22Na+ fluxes in the absence of calcium ions, induced by aggregation of receptors. This reaction was optimally studied in the presence of ouabain. When aggregation of the receptor was induced by reacting the cell-bound IgE with a multivalent antigen, the sodium flux was completely inhibited by univalent hapten. The sodium flux was also completely inhibited by 2 mM calcium. Aggregation-induced 45Ca2+ fluxes were observed in the presence of millimolar concentrations of external Ca2+, but not in its absence. Depolarization of the plasma membrane potential by the addition of potassium to the medium in the presence of calcium did not itself induce degranulation. In fact, aggregation of the receptors for IgE in the presence of high external potassium resulted in a greatly diminished degranulation. These data indicate that the ion channel modulated by aggregation of receptor differs from the voltage-dependent type of calcium channels. We suggest that in the absence of calcium this channel is rather unspecific, but that calcium can modify it to become calcium selective.
D000818:Animals; D001491:Basophils / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D007202:Indicators and Reagents; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000378:metabolism*; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017455:Receptors, IgE; D011971:Receptors, Immunologic / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D007202:Indicators and Reagents; D007473:Ion Channels; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D012701:Serotonin; D007073:Immunoglobulin E; D012964:Sodium; D011188:Potassium; D002118:Calcium; C013289:tetraphenylphosphonium