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J Gen Physiol. 2017 Mar 6;149(3):373-387. doi: 10.1085/jgp.201611646. Epub 2017 Feb 14.

Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels.

Author information

1
Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130.
2
Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136.
3
Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, Suzhou 215123, China.
4
Department of Anatomy and Neurobiology (Department of Neuroscience), Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
5
Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
6
Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University, St. Louis, MO 63130 jcui@wustl.edu.

Abstract

Large conductance Ca2+-activated K+ channels (BK channels) gate open in response to both membrane voltage and intracellular Ca2+ The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca2+ sensor. How these voltage and Ca2+ sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca2+ activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1313433110). In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca2+ sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel's β1 and β2 subunits.

PMID:
28196879
PMCID:
PMC5339509
DOI:
10.1085/jgp.201611646
[Indexed for MEDLINE]
Free PMC Article

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