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

Guohui Zhang, Yanyan Geng, Yakang Jin, Jingyi Shi, Kelli McFarland, Karl Magleby, Lawrence Salkoff, Jianmin Cui

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)373-387
Number of pages15
JournalThe Journal of general physiology
Volume149
Issue number3
DOIs
StatePublished - Mar 6 2017

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels
Intracellular Membranes
Membranes

ASJC Scopus subject areas

  • Physiology

Cite this

Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels. / Zhang, Guohui; Geng, Yanyan; Jin, Yakang; Shi, Jingyi; McFarland, Kelli; Magleby, Karl; Salkoff, Lawrence; Cui, Jianmin.

In: The Journal of general physiology, Vol. 149, No. 3, 06.03.2017, p. 373-387.

Research output: Contribution to journalArticle

Zhang, Guohui ; Geng, Yanyan ; Jin, Yakang ; Shi, Jingyi ; McFarland, Kelli ; Magleby, Karl ; Salkoff, Lawrence ; Cui, Jianmin. / Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels. In: The Journal of general physiology. 2017 ; Vol. 149, No. 3. pp. 373-387.
@article{89e92cc376f74ddeae4dd5dad6b45163,
title = "Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels",
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.",
author = "Guohui Zhang and Yanyan Geng and Yakang Jin and Jingyi Shi and Kelli McFarland and Karl Magleby and Lawrence Salkoff and Jianmin Cui",
year = "2017",
month = "3",
day = "6",
doi = "10.1085/jgp.201611646",
language = "English (US)",
volume = "149",
pages = "373--387",
journal = "Journal of General Physiology",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels

AU - Zhang, Guohui

AU - Geng, Yanyan

AU - Jin, Yakang

AU - Shi, Jingyi

AU - McFarland, Kelli

AU - Magleby, Karl

AU - Salkoff, Lawrence

AU - Cui, Jianmin

PY - 2017/3/6

Y1 - 2017/3/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85021760347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021760347&partnerID=8YFLogxK

U2 - 10.1085/jgp.201611646

DO - 10.1085/jgp.201611646

M3 - Article

C2 - 28196879

AN - SCOPUS:85021760347

VL - 149

SP - 373

EP - 387

JO - Journal of General Physiology

JF - Journal of General Physiology

SN - 0022-1295

IS - 3

ER -