Regulation of Lymphocyte Chloride Channels
The chloride permeability defect which characterizes the apical membrane of secretory epithelial cells in cystic fibrosis has been difficult to study in part because of lack of accessibility of tissue for study. This problem has fostered attempts by investigators both to immortalize epithelial cell lines and to search for other cells which may serve as a model to study chloride conductances. As we describe here, transformed lympho-blasts have whole cell chloride currents under conditions of stimulation by cAMP agonists, calcium ionophore, or hypotonicity which are quite similar to the aggregate chloride currents measured under similar conditions in epithelial cells. In addition, transformed B and malignant T cells have an outwardly rectifying, 40pS, chloride selective channel that is activated during patch clamp recording by one of at least three ways: 1) patch excision and depolarization; 2) phosphorylation by cAMP-dependent protein kinase (PKA); 3) by exposure of the lympho-blast to Ca2+ ionophore during cell-attached recording. This channel is closely similar or identical to the outwardly rectifying chloride channel identified by patch clamp recording from the apical membrane in secretory epithelial cells (Frizzell et al., 1986; Welsh, 1986; Welsh and Liedtke, 1986; Schoumacher et al., 1987; Li et al., 1988).
KeywordsCystic Fibrosis Chloride Channel Calcium Ionophore Patch Clamp Recording Secretory Epithelial Cell
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