Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1 , Kv8.2 , Slo1

Title: Phosphatidylinositol-4,5-Bisphosphate (PIP(2)) Stabilizes the Open Pore Conformation of the Kv11.1 (hERG) Channel.

Authors: Nicolas Rodriguez, Mohamed Yassine Amarouch, Jérôme Montnach, Julien Piron, Alain J Labro, Flavien Charpentier, Jean Mérot, Isabelle Baró, Gildas Loussouarn

Journal, date & volume: , 2010 Aug 9 , 99, 1110-1118

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20712994

Abstract
Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is a phospholipid that has been shown to modulate several ion channels, including some voltage-gated channels like Kv11.1 (hERG). From a biophysical perspective, the mechanisms underlying this regulation are not well characterized. From a physiological perspective, it is critical to establish whether the PIP(2) effect is within the physiological concentration range. Using the giant-patch configuration of the patch-clamp technique on COS-7 cells expressing hERG, we confirmed the activating effect of PIP(2). PIP(2) increased the hERG maximal current and concomitantly slowed deactivation. Regarding the molecular mechanism, these increased amplitude and slowed deactivation suggest that PIP(2) stabilizes the channel open state, as it does in KCNE1-KCNQ1. We used kinetic models of hERG to simulate the effects of the phosphoinositide. Simulations strengthened the hypothesis that PIP(2) is more likely stabilizing the channel open state than affecting the voltage sensors. From the physiological aspect, we established that the sensitivity of hERG to PIP(2) comes close to that of KCNE1-KCNQ1 channels, which lies in the range of physiological PIP(2) variations.