Skip to main content

Computational modelling elucidates the mechanism of ciliary regulation in health and disease

Kotov, Nikolay V., Bates, Declan G., Gizatullina, Antonina N., Gilaziev, Bulat, Khairullin, Rustem N, Chen, Michael ZQ, Drozdov, Ignat, Umezawa, Yoshinori, Hundhausen, Christian, Aleksandrov, Alexey, and others. (2011) Computational modelling elucidates the mechanism of ciliary regulation in health and disease. BMC Systems Biology, 5 . p. 143. ISSN 1752-0509. (doi:10.1186/1752-0509-5-143)

This is the latest version of this item.

Abstract

Background

Ciliary dysfunction leads to a number of human pathologies, including primary ciliary dyskinesia, nephronophthisis, situs inversus pathology or infertility. The mechanism of cilia beating regulation is complex and despite extensive experimental characterization remains poorly understood. We develop a detailed systems model for calcium, membrane potential and cyclic nucleotide-dependent ciliary motility regulation.

Results

The model describes the intimate relationship between calcium and potassium ionic concentrations inside and outside of cilia with membrane voltage and, for the first time, describes a novel type of ciliary excitability which plays the major role in ciliary movement regulation. Our model describes a mechanism that allows ciliary excitation to be robust over a wide physiological range of extracellular ionic concentrations. The model predicts the existence of several dynamic modes of ciliary regulation, such as the generation of intraciliary Ca2+ spike with amplitude proportional to the degree of membrane depolarization, the ability to maintain stable oscillations, monostable multivibrator regimes, all of which are initiated by variability in ionic concentrations that translate into altered membrane voltage.

Conclusions

Computational investigation of the model offers several new insights into the underlying molecular mechanisms of ciliary pathologies. According to our analysis, the reported dynamic regulatory modes can be a physiological reaction to alterations in the extracellular environment. However, modification of the dynamic modes, as a result of genetic mutations or environmental conditions, can cause a life threatening pathology.

Item Type: Article
DOI/Identification number: 10.1186/1752-0509-5-143
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Faculties > Sciences > School of Engineering and Digital Arts
Faculties > Sciences > School of Engineering and Digital Arts > Instrumentation, Control and Embedded Systems
Depositing User: Mark Smales
Date Deposited: 25 Nov 2013 12:53 UTC
Last Modified: 01 Aug 2019 10:36 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/36889 (The current URI for this page, for reference purposes)
Yan, Xinggang: https://orcid.org/0000-0003-2217-8398
Smales, Christopher Mark: https://orcid.org/0000-0002-2762-4724

Available versions of this item

  • Computational modelling elucidates the mechanism of ciliary regulation in health and disease. (deposited 25 Nov 2013 12:53) [Currently Displayed]
  • Depositors only (login required):

Downloads

Downloads per month over past year