Allosteric control of gating mechanisms revisited: the large conductance Ca2+-activated K+ channel.

Abstract:

:Large-conductance Ca(2+)-activated K(+) channels (BK) play a fundamental role in modulating membrane potential in many cell types. The gating of BK channels and its modulation by Ca(2+) and voltage has been the subject of intensive research over almost three decades, yielding several of the most complicated kinetic mechanisms ever proposed. A large number of open and closed states disposed, respectively, in two planes, named tiers, characterize these mechanisms. Transitions between states in the same plane are cooperative and modulated by Ca(2+). Transitions across planes are highly concerted and voltage-dependent. Here we reexamine the validity of the two-tiered hypothesis by restricting attention to the modulation by Ca(2+). Large single channel data sets at five Ca(2+) concentrations were simultaneously analyzed from a Bayesian perspective by using hidden Markov models and Markov-chain Monte Carlo stochastic integration techniques. Our results support a dramatic reduction in model complexity, favoring a simple mechanism derived from the Monod-Wyman-Changeux allosteric model for homotetramers, able to explain the Ca(2+) modulation of the gating process. This model differs from the standard Monod-Wyman-Changeux scheme in that one distinguishes when two Ca(2+) ions are bound to adjacent or diagonal subunits of the tetramer.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Rosales RA,Varanda WA

doi

10.1016/j.bpj.2009.02.042

subject

Has Abstract

pub_date

2009-05-20 00:00:00

pages

3987-96

issue

10

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)00593-1

journal_volume

96

pub_type

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