Permissive and nonpermissive channel closings in CFTR revealed by a factor graph inference algorithm

Alexander S Moffett; Guiying Cui; Peter J Thomas; William D Hunt; Nael A McCarty; Ryan S Westafer; Andrew W Eckford

doi:10.1016/j.bpr.2022.100083

Permissive and nonpermissive channel closings in CFTR revealed by a factor graph inference algorithm

Biophys Rep (N Y). 2022 Oct 19;2(4):100083. doi: 10.1016/j.bpr.2022.100083. eCollection 2022 Dec 14.

Authors

Alexander S Moffett¹, Guiying Cui², Peter J Thomas³, William D Hunt⁴, Nael A McCarty², Ryan S Westafer⁵, Andrew W Eckford¹

Affiliations

¹ Department of Electrical Engineering and Computer Science, York University, Toronto, ON, Canada.
² Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
³ Department of Mathematics, Applied Mathematics, and Statistics, Case Western Reserve University, Cleveland, Ohio.
⁴ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia.
⁵ Georgia Tech Research Institute, Atlanta, Georgia.

Abstract

The closing of the gated ion channel in the cystic fibrosis transmembrane conductance regulator can be categorized as nonpermissive to reopening, which involves the unbinding of ADP or ATP, or permissive, which does not. Identifying the type of closing is of interest as interactions with nucleotides can be affected in mutants or by introducing agonists. However, all closings are electrically silent and difficult to differentiate. For single-channel patch-clamp traces, we show that the type of the closing can be accurately determined by an inference algorithm implemented on a factor graph, which we demonstrate using both simulated and lab-obtained patch-clamp traces.