%0 Journal Article
%T Structural changes in the cytoplasmic pore of the Kir1.1 channel during pHi-gating probed by FRET
%A Jay-Ron Lee
%A Ru-Chi Shieh
%J Journal of Biomedical Science
%D 2009
%I BioMed Central
%R 10.1186/1423-0127-16-29
%X K+ homeostasis is controlled by the secretion of K+ ions across the apical membrane of cortical collecting duct cells in the kidney. Low-conductance inwardly rectifying K+ channels are the channels primarily responsible for K+ secretion [1,2]. These low-conductance K+ channels have been shown to be particularly sensitive to changes in the pHi. Intracellular acidification in the physiological range reversibly reduces the channel open probability and is thought to account for the subsequent decrease in K+ secretion [1-3]. Thus, the sensitivity of the apical K+ channel to the pHi is assumed to play a key role in K+ homeostasis.The processes involved in the opening and closing of Kir1.1 channels in response to pHi changes are not completely understood. It has been suggested that the closure of the Kir1.1 pHi gate results from the occlusion of the tetrameric channel pore by the convergence of four leucines at the cytoplasmic apexes of the four inner transmembrane helices [4]. In addition, it was recently proposed that H+ and PIP2 use a gating mechanism defined by conformational changes in the transmembrane helices and the selectivity filter and that the gating movement of the transmembrane helices is, in turn, controlled by an intrasubunit hydrogen bond between transmembrane domains 1 and 2 at the helix-bundle crossing [5].It has been proposed that ligands gating Kir channels open or close the pore by initiating conformational changes in the cytoplasmic domains [5]. The accessibility of N-terminal and C-terminal region cysteines C49 and C308 to methanethiosulfonate reagents has been shown to be pHi (state)-dependent, suggesting that pHi-gating may involve movements in the cytoplasmic-located pore, which is composed of both the N- and C-terminal regions [6]. Furthermore, the interaction of the N- and C-termini has been suggested to be an important part of the channel gating mechanism [7]. However, there is no direct evidence that the pHi can modulate the interaction of th
%U http://www.jbiomedsci.com/content/16/1/29