atp-sensitive potassium channels exhibit variance in the number of open channels below the limit predicted for identical and independent gatingatp-sensitive钾离子通道具有方差在打开的通道的数量低于限制相同的预测和独立控制.pdf

ATP-Sensitive Potassium Channels Exhibit Variance in the Number of Open Channels below the Limit Predicted for Identical and Independent Gating Kee-Hyun Choi¤a, Stuart Licht*¤b Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract In small cells containing small numbers of ion channels, noise due to stochastic channel opening and closing can introduce a substantial level of variability into the cell’s membrane potential. Negatively cooperative interactions that couple a channel’s gating conformational change to the conformation of its neighbor(s) provide a potential mechanism for mitigating this variability, but such interactions have not previously been directly observed. Here we show that heterologously expressed ATP-sensitive potassium channels generate noise (i.e., variance in the number of open channels) below the level possible for identical and independent channels. Kinetic analysis with single-molecule resolution supports the interpretation that interchannel negative cooperativity (specifically, the presence of an open channel making a closed channel less likely to open) contributes to the decrease in noise. Functional coupling between channels may be important in modulating stochastic fluctuations in cellular signaling pathways. Citation: Choi K-H, Licht S (2012) ATP-Sensitive Potassium Channels Exhibit Variance in the Number of Open Channels below the Limit Predicted for Identical and Independent Gating. PLoS ONE 7(5): e37399. doi:10.1371/journal.pone.0037399 Editor: Floyd Romesberg, The Scripps Research Institute, United States of America Received July 5, 2011; Accepted April 22, 2012; Published May 30, 2012 Copyright: 2012 Choi, Licht. This is an open-access article distributed under the te