Silent TWIK-1 Potassium Channels Conduct Monovalent Cation Currents

TWIK-1 two-pore domain K+ channels generally produce nonmeasurable or very low levels of K+ currents in heterologous expression systems under physiologically ionic conditions. Two controversial mechanisms have been proposed to account for this behavior: TWIK-1 K+ channels are expressed in the cell surface but silenced by sumoylation at a lysine residue (TWIK-1 K274); constitutive and rapid internalization of TWIK-1 causes TWIK-1 channel silencing. Here we report that TWIK-1 K+ channels heterologously expressed in Chinese hamster ovary cells, which are silent in physiological K+ gradients, are able to conduct large monovalent cation currents when extracellular ionic conditions change. These results support the hypothesis that TWIK-1 K+ channels are expressed in the cell surface but silent, and suggest that the TWIK-1 gating behavior rather than the lack of cell surface expression of TWIK-1 results in nondetectable TWIK-1 K+ currents in heterologous expression systems.