| Full text | |
| Author(s): |
Total Authors: 2
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| Affiliation: | [1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret, Dept Math & Phys, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Physiol, BR-14049 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
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| Document type: | Journal article |
| Source: | BIOPHYSICAL JOURNAL; v. 96, n. 10, p. 3987-3996, MAY 20 2009. |
| Web of Science Citations: | 2 |
| Abstract | |
Large-conductance Ca2+-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 Ca2+ 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 Ca2+. 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 Ca2+. Large single channel data sets at five Ca2+ 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 Ca2+ modulation of the gating process. This model differs from the standard Monod-Wyman-Changeux scheme in that one distinguishes when two Ca2+ ions are bound to adjacent or diagonal subunits of the tetramer. (AU) | |
| FAPESP's process: | 05/02063-3 - Estimation of the infinitesimal generator of ion channel dynamics |
| Grantee: | Rafael Andres Rosales Mitrowsky |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 06/50954-7 - Ionic currents and receptors in the physiology of excitable and non-excitable cells |
| Grantee: | Wamberto Antonio Varanda |
| Support Opportunities: | Research Projects - Thematic Grants |