Endogenous ion channels expressed in human embryonic kidney (HEK-293) cells

Mammalian expression systems, particularly the human embryonic kidney (HEK-293) cells, combined with electrophysiological studies, have greatly benefited our understanding of the function, characteristic, and regulation of various ion channels. It was previously assumed that the existence of endogenous ion channels in native HEK-293 cells could be negligible. Still, more and more ion channels are gradually reported in native HEK-293 cells, which should draw our attention. In this regard, we summarize the different ion channels that are endogenously expressed in HEK-293 cells, including voltage-gated Na+ channels, Ca2+ channels, K+ channels, Cl- channels, nonselective cation channels, TRP channels, acid-sensitive ion channels, and Piezo channels, which may complicate the recording of the heterogeneously expressed ion channels to a certain degree. We noted that the expression patterns and channel profiles varied with different studies, which may be due to the distinct originality of the cells, cell culture conditions, passage numbers, and different recording protocols. Therefore, a better knowledge of endogenous ion channels may help minimize potential problems in characterizing heterologously expressed ion channels. Based on this, it is recommended that HEK-293 cells from unknown sources should be examined before transfection for the characterization of their functional profile, especially when the expression level of exogenous ion channels does not overwhelm the endogenous ion channels largely, or the current amplitude is not significantly higher than the native currents.

Automated summary

Mammalian expression systems, particularly HEK-293 cells, combined with electrophysiological studies, have greatly improved our understanding of ion channels. It was previously assumed that endogenous ion channels in HEK-293 cells were negligible, but recent studies have shown their presence should be considered. This article summarizes the different endogenously expressed ion channels in HEK-293 cells and highlights the variability in expression patterns and channel profiles. A better understanding of endogenous ion channels can help minimize potential issues in characterizing heterologously expressed ion channels. It is recommended to examine the functional profile of HEK-293 cells before transfection, especially when endogenous ion channels are not overwhelmed by exogenous ion channels.