Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2008 Jun 01;9412:4678-87. doi: 10.1529/biophysj.107.121590.
Show Gene links
Show Anatomy links
Subunit-specific effect of the voltage sensor domain on Ca2+ sensitivity of BK channels.
Yang H
,
Zhang G
,
Shi J
,
Lee US
,
Delaloye K
,
Cui J
.
???displayArticle.abstract???
Large conductance Ca(2+)- and voltage-activated K(+) (BK) channels, composed of pore-forming alpha-subunits and auxiliary beta-subunits, play important roles in diverse physiological processes. The differences in BK channel phenotypes are primarily due to the tissue-specific expression of beta-subunits (beta1-beta4) that modulate channel function differently. Yet, the molecular basis of the subunit-specific regulation is not clear. In our study, we demonstrate that perturbation of the voltage sensor in BK channels by mutations selectively disrupts the ability of the beta1-subunit--but not that of the beta2-subunit--to enhance apparent Ca(2+) sensitivity. These mutations change the number of equivalent gating charges, the voltage dependence of voltage sensor movements, the open-close equilibrium of the channel, and the allosteric coupling between voltage sensor movements and channel opening to various degrees, indicating that they alter the conformation and movements of the voltage sensor and the activation gate. Similarly, the ability of the beta1-subunit to enhance apparent Ca(2+) sensitivity is diminished to various degrees, correlating quantitatively with the shift of voltage dependence of voltage sensor movements. In contrast, none of these mutations significantly reduces the ability of the beta2-subunit to enhance Ca(2+) sensitivity. These results suggest that the beta1-subunit enhances Ca(2+) sensitivity by altering the conformation and movements of the voltage sensor, whereas the similar function of the beta2-subunit is governed by a distinct mechanism.
Adelman,
Calcium-activated potassium channels expressed from cloned complementary DNAs.
1992,
Pubmed
,
Xenbase
Atkinson,
A component of calcium-activated potassium channels encoded by the Drosophila slo locus.
1991,
Pubmed
Bao,
Gating and ionic currents reveal how the BKCa channel's Ca2+ sensitivity is enhanced by its beta1 subunit.
2005,
Pubmed
,
Xenbase
Bezanilla,
The voltage sensor in voltage-dependent ion channels.
2000,
Pubmed
Brenner,
Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.
2000,
Pubmed
Brenner,
Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
2000,
Pubmed
Butler,
mSlo, a complex mouse gene encoding "maxi" calcium-activated potassium channels.
1993,
Pubmed
,
Xenbase
Cox,
Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. Mechanisms of enhanced Ca(2+) sensitivity.
2000,
Pubmed
,
Xenbase
Cui,
Allosteric linkage between voltage and Ca(2+)-dependent activation of BK-type mslo1 K(+) channels.
2000,
Pubmed
Fettiplace,
Mechanisms of hair cell tuning.
1999,
Pubmed
Giangiacomo,
Functional reconstitution of the large-conductance, calcium-activated potassium channel purified from bovine aortic smooth muscle.
1995,
Pubmed
Herrera,
Regulation of urinary bladder smooth muscle contractions by ryanodine receptors and BK and SK channels.
2000,
Pubmed
Hicks,
Ca2+-dependent inactivation of large conductance Ca2+-activated K+ (BK) channels in rat hippocampal neurones produced by pore block from an associated particle.
1998,
Pubmed
Horrigan,
Allosteric voltage gating of potassium channels II. Mslo channel gating charge movement in the absence of Ca(2+).
1999,
Pubmed
Horrigan,
Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels.
2002,
Pubmed
,
Xenbase
Horrigan,
Allosteric voltage gating of potassium channels I. Mslo ionic currents in the absence of Ca(2+).
1999,
Pubmed
,
Xenbase
Khan,
Properties of large-conductance K+ channels in human myometrium during pregnancy and labour.
1993,
Pubmed
Knaus,
Primary sequence and immunological characterization of beta-subunit of high conductance Ca(2+)-activated K+ channel from smooth muscle.
1994,
Pubmed
Ledoux,
Calcium-activated potassium channels and the regulation of vascular tone.
2006,
Pubmed
Ma,
Role of charged residues in the S1-S4 voltage sensor of BK channels.
2006,
Pubmed
,
Xenbase
McManus,
Functional role of the beta subunit of high conductance calcium-activated potassium channels.
1995,
Pubmed
,
Xenbase
Morrow,
Defining the BK channel domains required for beta1-subunit modulation.
2006,
Pubmed
Nelson,
Physiological roles and properties of potassium channels in arterial smooth muscle.
1995,
Pubmed
Nimigean,
Functional coupling of the beta(1) subunit to the large conductance Ca(2+)-activated K(+) channel in the absence of Ca(2+). Increased Ca(2+) sensitivity from a Ca(2+)-independent mechanism.
2000,
Pubmed
Nimigean,
The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states.
1999,
Pubmed
Orio,
Differential effects of beta 1 and beta 2 subunits on BK channel activity.
2005,
Pubmed
,
Xenbase
Orio,
Structural determinants for functional coupling between the beta and alpha subunits in the Ca2+-activated K+ (BK) channel.
2006,
Pubmed
,
Xenbase
Qian,
Slo1 tail domains, but not the Ca2+ bowl, are required for the beta 1 subunit to increase the apparent Ca2+ sensitivity of BK channels.
2002,
Pubmed
,
Xenbase
Salkoff,
High-conductance potassium channels of the SLO family.
2006,
Pubmed
Savalli,
Modes of operation of the BKCa channel beta2 subunit.
2007,
Pubmed
,
Xenbase
Semenov,
BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle.
2006,
Pubmed
Shen,
Tetraethylammonium block of Slowpoke calcium-activated potassium channels expressed in Xenopus oocytes: evidence for tetrameric channel formation.
1994,
Pubmed
,
Xenbase
Swartz,
Towards a structural view of gating in potassium channels.
2004,
Pubmed
Toro,
Maxi-K(Ca), a Unique Member of the Voltage-Gated K Channel Superfamily.
1998,
Pubmed
Torres,
A marriage of convenience: beta-subunits and voltage-dependent K+ channels.
2007,
Pubmed
Uebele,
Cloning and functional expression of two families of beta-subunits of the large conductance calcium-activated K+ channel.
2000,
Pubmed
Wallner,
Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog.
1999,
Pubmed
,
Xenbase
Wallner,
Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus.
1996,
Pubmed
Wang,
An S6 mutation in BK channels reveals beta1 subunit effects on intrinsic and voltage-dependent gating.
2006,
Pubmed
Xia,
Inactivation of BK channels by the NH2 terminus of the beta2 auxiliary subunit: an essential role of a terminal peptide segment of three hydrophobic residues.
2003,
Pubmed
,
Xenbase
Xia,
Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells.
1999,
Pubmed
,
Xenbase
Yellen,
The voltage-gated potassium channels and their relatives.
2002,
Pubmed
