Dissociation of depolarization-activated and swelling-activated Cl- channels

In many cells, patch excision and depolarization induce outwardly rectifying Cl- channels (ORDIC channels) whose function and normal mode of regulation are unknown. One possible function is the mediation of swelling-activated Cl- conductance, because in many cells rectifying Cl- currents are activated by cell swelling. However, swelling-activated Cl- channels in some epithelia have larger conductances than ORDIC channels and inactivate more rapidly, although both have similar anion selectivity and are blocked by stilbenes. Thus it has not been possible to determine whether the two types of channel current arise from distinct proteins or alternate states of a single protein. We studied 14 cell lines and found 2 lines, C127 mouse mammary epithelial cells and IEC-6 rat intestinal crypt cells, with very low levels of ORDIC channels. However, despite the near absence of ORDIC channels in these rodent cells, a large swelling-activated Cl-conductance was demonstrated by whole cell, efflux, and single-channel methods. Thus it is likely that ORDIC and swelling-activated channel currents arise from different channel proteins.