The Journal of General Physiology
Cardiac Regulatory Mechanisms Conference
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online Sep 25 2006. doi:10.1085/jgp.200609486
The Rockefeller University Press, 0022-1295 $8.00
JGP, Volume 128, Number 4, 389-404
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Correction (v128,p629)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JGP
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qian, X.
Right arrow Articles by Magleby, K. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qian, X.
Right arrow Articles by Magleby, K. L.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Intra- and Intersubunit Cooperativity in Activation of BK Channels by Ca2+



Xiang Qian, Xiaowei Niu, and Karl L. Magleby

Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL 33101

Correspondence to Xiang Qian: xiang.qian{at}ucsf.edu; or Karl Magleby: kmagleby{at}miami.edu

The activation of BK channels by Ca2+ is highly cooperative, with small changes in intracellular Ca2+ concentration having large effects on open probability (Po). Here we examine the mechanism of cooperative activation of BK channels by Ca2+. Each of the four subunits of BK channels has a large intracellular COOH terminus with two different high-affinity Ca2+ sensors: an RCK1 sensor (D362/D367) located on the RCK1 (regulator of conductance of K+) domain and a Ca-bowl sensor located on or after the RCK2 domain. To determine interactions among these Ca2+ sensors, we examine channels with eight different configurations of functional high-affinity Ca2+ sensors on the four subunits. We find that the RCK1 sensor and Ca bowl contribute about equally to Ca2+ activation of the channel when there is only one high-affinity Ca2+ sensor per subunit. We also find that an RCK1 sensor and a Ca bowl on the same subunit are much more effective in increasing Po than when they are on different subunits, indicating positive intrasubunit cooperativity. If it is assumed that BK channels have a gating ring similar to MthK channels with alternating RCK1 and RCK2 domains and that the Ca2+ sensors act at the flexible (rather than fixed) interfaces between RCK domains, then a comparison of the distribution of Ca2+ sensors with the observed responses suggest that the interface between RCK1 and RCK2 domains on the same subunit is flexible. On this basis, intrasubunit cooperativity arises because two high-affinity Ca2+ sensors acting across a flexible interface are more effective in opening the channel than when acting at separate interfaces. An allosteric model incorporating intrasubunit cooperativity nested within intersubunit cooperativity could approximate the Po vs. Ca2+ response for eight possible subunit configurations of the high-affinity Ca2+ sensors as well as for three additional configurations from a previous study.

Xiang Qian's present address is Howard Hughes Medical Institute and Departments of Physiology and Biochemistry, University of California, San Francisco, CA 94143.

Abbreviations used in this paper: BK channel, large conductance Ca2+- and voltage-activated K+ channel; Ca2+i, intracellular Ca2+; RCK, regulator of the conductance of potassium; WT, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

A Tail of Multiple Calcium-sensing Domains
Lawrence Salkoff
J. Gen. Physiol. 2006 128: 387-388. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Biophys. JHome page
H.-J. Kim, H.-H. Lim, S.-H. Rho, L. Bao, J.-H. Lee, D. H. Cox, D. H. Kim, and C.-S. Park
Modulation of the Conductance-Voltage Relationship of the BKCa Channel by Mutations at the Putative Flexible Interface between Two RCK Domains
Biophys. J., January 15, 2008; 94(2): 446 - 456.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Yusifov, N. Savalli, C. S. Gandhi, M. Ottolia, and R. Olcese
The RCK2 domain of the human BKCa channel is a calcium sensor
PNAS, January 8, 2008; 105(1): 376 - 381.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
N. Savalli, A. Kondratiev, S. B. de Quintana, L. Toro, and R. Olcese
Modes of Operation of the BKCa Channel {beta}2 Subunit
J. Gen. Physiol., July 1, 2007; 130(1): 117 - 131.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
C. J. Lingle
Gating Rings Formed by RCK Domains: Keys to Gate Opening
J. Gen. Physiol., February 2, 2007; 129(2): 101 - 107.
[Full Text] [PDF]

Home page
 PhysiologyHome page
Highlights From The Literature
Physiology, February 1, 2007; 22(1): 3 - 6.
[Full Text] [PDF]


  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents