Biophys J. 2012 Apr 18;102(8):L34-6. doi: 10.1016/j.bpj.2012.03.011.
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.
TWIK-1 双孔钾通道在生理离子条件下的异源表达系统中通常产生可测或极低水平的钾电流。有两种有争议的机制被提出来解释这种行为：TWIK-1 钾通道在细胞表面表达，但在赖氨酸残基（TWIK-1 K274）处被 sumoylation 沉默；TWIK-1 的组成性和快速内化导致 TWIK-1 通道沉默。在这里，我们报告在中华仓鼠卵巢细胞中异源表达的 TWIK-1 钾通道在生理钾梯度中是沉默的，但当细胞外离子条件发生变化时，它们能够传导大的单价阳离子电流。这些结果支持 TWIK-1 钾通道在细胞表面表达但沉默的假设，并表明 TWIK-1 门控行为而不是 TWIK-1 缺乏细胞表面表达导致异源表达系统中无法检测到 TWIK-1 钾电流。
