PubMed 24277843

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv1.2 , Kv7.2

Title: Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating.

Authors: Qiansen Zhang, Pingzheng Zhou, Zhuxi Chen, Min Li, Hualiang Jiang, Zhaobing Gao, Huaiyu Yang

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2013 Dec 10 , 110, 20093-8

PubMed link:

The S4 segment and the S4-S5 linker of voltage-gated potassium (Kv) channels are crucial for voltage sensing. Previous studies on the Shaker and Kv1.2 channels have shown that phosphatidylinositol-4,5-bisphosphate (PIP2) exerts opposing effects on Kv channels, up-regulating the current amplitude, while decreasing the voltage sensitivity. Interactions between PIP2 and the S4 segment or the S4-S5 linker in the closed state have been highlighted to explain the effects of PIP2 on voltage sensitivity. Here, we show that PIP2 preferentially interacts with the S4-S5 linker in the open-state KCNQ2 (Kv7.2) channel, whereas it contacts the S2-S3 loop in the closed state. These interactions are different from the PIP2-Shaker and PIP2-Kv1.2 interactions. Consistently, PIP2 exerts different effects on KCNQ2 relative to the Shaker and Kv1.2 channels; PIP2 up-regulates both the current amplitude and voltage sensitivity of the KCNQ2 channel. Disruption of the interaction of PIP2 with the S4-S5 linker by a single mutation decreases the voltage sensitivity and current amplitude, whereas disruption of the interaction with the S2-S3 loop does not alter voltage sensitivity. These results provide insight into the mechanism of PIP2 action on KCNQ channels. In the closed state, PIP2 is anchored at the S2-S3 loop; upon channel activation, PIP2 interacts with the S4-S5 linker and is involved in channel gating.