Regulation of the murine TRPP3 channel by voltage, pH, and changes in cell volume

Transient receptor potential (TRP) polycystin 3 (TRPP3) is a member of the TRP superfamily of cation channels. Murine TRPP3 has been reported to form an acid-activated cation channel on the plasma membrane when coexpressed with the polycystin 1-like protein 3 (PKD1L3); however, the function and biophysical properties of TRPP3-dependent channels have not yet been characterized in detail. Here we show that overexpression of murine TRPP3 channel in HEK293 cells, without coexpression of PDK1-like proteins, leads to robust channel activity. These channels exhibit a high single-channel conductance of 184 pS at negative potentials, are Ca2+-permeable, and relatively nonselective between cations. Whole-cell experiments showed a characteristic form of voltage-dependent gating of TRPP3 channels, whereby repolarization after depolarization caused large transient inward TRPP3 tail currents. Moreover, we found that TRPP3 activity was increased upon cell swelling and by alkalization. Taken together, our results demonstrate that TRPP3, on its own, can act as a voltage-dependent, pH- and volume-sensitive plasma membrane cation channel.