The chloride current induced by expression of the protein pICln in Xenopus oocytes differs from the endogenous volume-sensitive chloride current.

1. Phenotypical similarities between ICl,swell, the cell-swelling-induced chloride current and ICln, the nucleotide-sensitive chloride current induced by expression of mammalian pICln in Xenopus oocytes, have led to models which identify pICln either as the volume-sensitive chloride channel or as a cytosolic regulator thereof. 2. To investigate critically the relationship between ICl,swell and pICln two-microelectrode voltage clamp experiments were performed on Xenopus oocytes in which either human pICln was expressed or endogenous ICl,swell was activated. 3. Several criteria that clearly differentiated ICln from ICl,swell were detected. Outward rectification and the discrimination between NO3- and Cl- were more pronounced for ICln. Cyclamate blocked ICln but not ICl,swell. In contrast to ICl,swell, inactivation kinetics of ICln were pH independent and extracellular cAMP blocked only the outward ICln component. Finally, ICln was readily expressed in collagenase-defolliculated oocytes and was not modulated by extracellular hypotonicity, whereas ICl,swell could only be triggered in follicle-enclosed or manually defolliculated oocytes. 4. We therefore conclude that ICln and ICl,swell are two different chloride currents. Consequently, any model which invokes a crucial role for pICln in ICl,swell should be critically reviewed.