Identifying Swelling-activated Channels from Ion Selectivity Patterns

The molecular identity of the channels producing swelling-activated Cl conductance (gswell) is of great interest since this physiologic response to swelling is common to many cells. As presented in the May Perspectives (Clapham, 1998; Strange, 1998), the question of whether the observed gswell represents a family of channel proteins is presently unanswered, but to be included in this family a channel must be activated by cell swelling and conduct Cl. Determining if a candidate Cl channel should be included based on swelling sensitivity may be problematic since the volume-sensing element could reside in an auxiliary protein that associates with the channel protein and, through allosteric modulation, creates a swelling-activated complex. If the associated sensor is removed inadvertently by experimental manipulation or incomplete reconstitution, then a legitimate family member would be excluded. Permeation selectivity is intrinsic to the pore of the channel protein and thus provides a less easily lost characteristic to aid in identification.