Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the α subunit

A study of mSlo1 and mSlo3 wild-type and chimeric channels

Brenda L. Moss, Karl Magleby

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The COOH-terminal S9-S10 tail domain of large conductance Ca2+-activated K+ (BK) channels is a major determinant of Ca2+ sensitivity (Schreiber, M., A. Wei, A. Yuan, J. Gaut, M. Saito, and L. Salkoff. 1999. Nat. Neurosci. 2:416-421). To investigate whether the tail domain also modulates Ca2+-independent properties of BK channels, we explored the functional differences between the BK channel mSlol and another member of the Slo family, mSlo3 (Schreiber, M., A. Yuan, and L. Salkoff. 1998. J. Biol. Chem. 273:3509-3516). Compared with mSlo1 channels, mSlo3 channels showed little Ca2+ sensitivity, and the mean open time, burst duration, gaps between bursts, and single-channel conductance of mSlo3 channels were only 32, 22, 41, and 37% of that for mSlol channels, respectively. To examine which channel properties arise from the tail domain, we coexpressed the core of mSlo1 with either the tail domain of mSlo3 or the tail domain of mSlo3 channels, and studied the single-channel currents. Replacing the mSlo1 tail with the mSlo3 tail resulted in the following: increased open probability in the absence of Ca2+; reduced the Ca2+ sensitivity greatly by allowing only partial activation by Ca2+ and by reducing the Hill coefficient for Ca2+ activation; decreased the voltage dependence ∼28%; decreased the mean open time two- to threefold; decreased the mean burst duration three- to ninefold; decreased the single-channel conductance ∼14%; decreased the Kd for block by TEA, ∼30%; did not change the minimal numbers of three to four open and five to seven closed states entered during gating; and did not change the major features of the dependency between adjacent interval durations. These observations support a modular construction of the BK channel in which the tail domain modulates the gating kinetics and conductance properties of the voltage-dependent core domain, in addition to determining most of the high affinity Ca2+ sensitivity.

Original languageEnglish
Pages (from-to)711-734
Number of pages24
JournalJournal of General Physiology
Volume118
Issue number6
DOIs
StatePublished - Dec 22 2001

Fingerprint

S 10
Large-Conductance Calcium-Activated Potassium Channels
Calcium-Activated Potassium Channels

Keywords

  • Ca-activated K channel
  • Gating kinetics
  • Maxi K channel
  • MWC model
  • TEA

ASJC Scopus subject areas

  • Physiology

Cite this

@article{93cf4fed928a48cdad701fe12a780134,
title = "Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the α subunit: A study of mSlo1 and mSlo3 wild-type and chimeric channels",
abstract = "The COOH-terminal S9-S10 tail domain of large conductance Ca2+-activated K+ (BK) channels is a major determinant of Ca2+ sensitivity (Schreiber, M., A. Wei, A. Yuan, J. Gaut, M. Saito, and L. Salkoff. 1999. Nat. Neurosci. 2:416-421). To investigate whether the tail domain also modulates Ca2+-independent properties of BK channels, we explored the functional differences between the BK channel mSlol and another member of the Slo family, mSlo3 (Schreiber, M., A. Yuan, and L. Salkoff. 1998. J. Biol. Chem. 273:3509-3516). Compared with mSlo1 channels, mSlo3 channels showed little Ca2+ sensitivity, and the mean open time, burst duration, gaps between bursts, and single-channel conductance of mSlo3 channels were only 32, 22, 41, and 37{\%} of that for mSlol channels, respectively. To examine which channel properties arise from the tail domain, we coexpressed the core of mSlo1 with either the tail domain of mSlo3 or the tail domain of mSlo3 channels, and studied the single-channel currents. Replacing the mSlo1 tail with the mSlo3 tail resulted in the following: increased open probability in the absence of Ca2+; reduced the Ca2+ sensitivity greatly by allowing only partial activation by Ca2+ and by reducing the Hill coefficient for Ca2+ activation; decreased the voltage dependence ∼28{\%}; decreased the mean open time two- to threefold; decreased the mean burst duration three- to ninefold; decreased the single-channel conductance ∼14{\%}; decreased the Kd for block by TEA, ∼30{\%}; did not change the minimal numbers of three to four open and five to seven closed states entered during gating; and did not change the major features of the dependency between adjacent interval durations. These observations support a modular construction of the BK channel in which the tail domain modulates the gating kinetics and conductance properties of the voltage-dependent core domain, in addition to determining most of the high affinity Ca2+ sensitivity.",
keywords = "Ca-activated K channel, Gating kinetics, Maxi K channel, MWC model, TEA",
author = "Moss, {Brenda L.} and Karl Magleby",
year = "2001",
month = "12",
day = "22",
doi = "10.1085/jgp.118.6.711",
language = "English",
volume = "118",
pages = "711--734",
journal = "Journal of General Physiology",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the α subunit

T2 - A study of mSlo1 and mSlo3 wild-type and chimeric channels

AU - Moss, Brenda L.

AU - Magleby, Karl

PY - 2001/12/22

Y1 - 2001/12/22

N2 - The COOH-terminal S9-S10 tail domain of large conductance Ca2+-activated K+ (BK) channels is a major determinant of Ca2+ sensitivity (Schreiber, M., A. Wei, A. Yuan, J. Gaut, M. Saito, and L. Salkoff. 1999. Nat. Neurosci. 2:416-421). To investigate whether the tail domain also modulates Ca2+-independent properties of BK channels, we explored the functional differences between the BK channel mSlol and another member of the Slo family, mSlo3 (Schreiber, M., A. Yuan, and L. Salkoff. 1998. J. Biol. Chem. 273:3509-3516). Compared with mSlo1 channels, mSlo3 channels showed little Ca2+ sensitivity, and the mean open time, burst duration, gaps between bursts, and single-channel conductance of mSlo3 channels were only 32, 22, 41, and 37% of that for mSlol channels, respectively. To examine which channel properties arise from the tail domain, we coexpressed the core of mSlo1 with either the tail domain of mSlo3 or the tail domain of mSlo3 channels, and studied the single-channel currents. Replacing the mSlo1 tail with the mSlo3 tail resulted in the following: increased open probability in the absence of Ca2+; reduced the Ca2+ sensitivity greatly by allowing only partial activation by Ca2+ and by reducing the Hill coefficient for Ca2+ activation; decreased the voltage dependence ∼28%; decreased the mean open time two- to threefold; decreased the mean burst duration three- to ninefold; decreased the single-channel conductance ∼14%; decreased the Kd for block by TEA, ∼30%; did not change the minimal numbers of three to four open and five to seven closed states entered during gating; and did not change the major features of the dependency between adjacent interval durations. These observations support a modular construction of the BK channel in which the tail domain modulates the gating kinetics and conductance properties of the voltage-dependent core domain, in addition to determining most of the high affinity Ca2+ sensitivity.

AB - The COOH-terminal S9-S10 tail domain of large conductance Ca2+-activated K+ (BK) channels is a major determinant of Ca2+ sensitivity (Schreiber, M., A. Wei, A. Yuan, J. Gaut, M. Saito, and L. Salkoff. 1999. Nat. Neurosci. 2:416-421). To investigate whether the tail domain also modulates Ca2+-independent properties of BK channels, we explored the functional differences between the BK channel mSlol and another member of the Slo family, mSlo3 (Schreiber, M., A. Yuan, and L. Salkoff. 1998. J. Biol. Chem. 273:3509-3516). Compared with mSlo1 channels, mSlo3 channels showed little Ca2+ sensitivity, and the mean open time, burst duration, gaps between bursts, and single-channel conductance of mSlo3 channels were only 32, 22, 41, and 37% of that for mSlol channels, respectively. To examine which channel properties arise from the tail domain, we coexpressed the core of mSlo1 with either the tail domain of mSlo3 or the tail domain of mSlo3 channels, and studied the single-channel currents. Replacing the mSlo1 tail with the mSlo3 tail resulted in the following: increased open probability in the absence of Ca2+; reduced the Ca2+ sensitivity greatly by allowing only partial activation by Ca2+ and by reducing the Hill coefficient for Ca2+ activation; decreased the voltage dependence ∼28%; decreased the mean open time two- to threefold; decreased the mean burst duration three- to ninefold; decreased the single-channel conductance ∼14%; decreased the Kd for block by TEA, ∼30%; did not change the minimal numbers of three to four open and five to seven closed states entered during gating; and did not change the major features of the dependency between adjacent interval durations. These observations support a modular construction of the BK channel in which the tail domain modulates the gating kinetics and conductance properties of the voltage-dependent core domain, in addition to determining most of the high affinity Ca2+ sensitivity.

KW - Ca-activated K channel

KW - Gating kinetics

KW - Maxi K channel

KW - MWC model

KW - TEA

UR - http://www.scopus.com/inward/record.url?scp=0035200399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035200399&partnerID=8YFLogxK

U2 - 10.1085/jgp.118.6.711

DO - 10.1085/jgp.118.6.711

M3 - Article

VL - 118

SP - 711

EP - 734

JO - Journal of General Physiology

JF - Journal of General Physiology

SN - 0022-1295

IS - 6

ER -