Crosslinking of the receptors for immunoglobulin E depolarizes the plasma membrane of rat basophilic leukemia cells.

Aggregation of the receptor for IgE on mast cells, basophils, and a tumor analog, rat basophilic leukemia (RBL) cells, induces a calcium-dependent degranulation of the cells. We have measured the membrane potential (delta psi) of RBL cells during this reaction by using the tetraphenylphosphonium ion (Ph4P+) equilibration technique. We observed a 20-45% reduction in ionophore-sensitive Ph4P+ accumulation. The phenomenon persisted under conditions expected to collapse the mitochondrial membrane potential, consistent with the effect being due to a change in delta psi of the plasma membrane. We estimated that the change reflects a depolarization of 20 mV (from -90 to -70 mV, interior negative). Whereas degranulation fails to occur in the absence of external Ca2+, this was not true of the depolarization, indicating that the latter was not a consequence of secretion. When aggregation of the receptor is induced by reaction of the cell-bound IgE with a multivalent antigen, the secretory reaction can be halted by adding a univalent hapten. In this case, complete repolarization occurs. Equivalent depolarization was observed in the absence of Na+ but was diminished when both Ca2+ and Na+ were absent. Together, the data suggest that aggregation of the receptor opens ion channels and that the latter disappear promptly when the receptors are disaggregated. It is plausible that formation of these channels leads to the entry of Ca2+ and is an early and critical consequence of the aggregation of the receptors, thereby leading to degranulation.