Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells

The detection of changes in volume and osmolatity is an essential function in vertebrate cells. A novel member of the transient receptor potential (tr p) family of ion channels, which is sensitive to changes in cell volume, ha s been described recently. Heterologous expression of TRP12 in HEK cells re sulted in the appearance of a swelling-activated cation current. The permea bility sequence of this cation current for various monovalent cations, as d etermined from shifts in reversal potential upon extracellular cation subst itution, was P-K>P-Cs>P-Na>P-Li, corresponding to an Eisenman-IV sequence c haracteristic for a weak-field-strength site. Surprisingly, over-expression of this channel in HEK cells was accompanied by a dramatic down-regulation of the volume-regulated anion channel (VRAC), which is activated by cell s welling in non-transfected cells. In contrast to VRAC. TRP12 could not be a ctivated at constant volume by a reduction of intracellular ionic strength or by intracellular perfusion with guanosine 5'-O-(3 -thiotriphosphate (GTP gammaS). The kinetic and pharmacological profile of VRAC and TRP12 current s were also different.