TY - JOUR
T1 - Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening
AU - Hou, Panpan
AU - Eldstrom, Jodene
AU - Shi, Jingyi
AU - Zhong, Ling
AU - McFarland, Kelli
AU - Gao, Yuan
AU - Fedida, David
AU - Cui, Jianmin
N1 - Funding Information:
We thank Dr S. Goldstein (Brandeis University) for the KCNQ1 clone, and Dr N. Schmitt for the GFP-tagged KCNQ1. We thank Dr M. Zaydman for initiating the study and helpful discussions during manuscript writing, and Professor James Ballard for proofreading of the manuscript. We thank Dr F. Xiao for the valuable suggestions on channel modeling. This work was supported by National Institutes of Health Grants R01 NS092570 and R01HL126774 to J.C. and grant number G-14-0006091 from the Heart and Stroke Foundation of Canada to D.F.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation.
AB - In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation.
UR - http://www.scopus.com/inward/record.url?scp=85034986778&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01911-8
DO - 10.1038/s41467-017-01911-8
M3 - Article
C2 - 29167462
AN - SCOPUS:85034986778
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1730
ER -