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Excitability constraints on voltage-gated sodium channels
Elaine Angelino1, Michael P Brenner
1Systems Biology Graduate Program, Harvard University, Cambridge, Massachusetts, USA.
Plos Computational Biology
|September 26, 2007
Summary
Functional constraints shape the evolution of mammalian voltage-gated sodium channels. Despite high sequence similarity, distinct functional groups emerge, explaining the diversity of these essential ion channels.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Neuroscience
Background:
- Mammalian voltage-gated sodium channels are crucial for action potential propagation.
- Mathematical models indicate tight constraints on sodium channel properties for excitability.
- Nine mammalian genes encode sodium channels, many with high sequence identity.
Purpose of the Study:
- To investigate how functional constraints shape the evolution and diversity of mammalian voltage-gated sodium channels.
- To determine if theoretical constraints explain the multiplicity of sodium channel genes.
Main Methods:
- Analysis of functional data from 172 measurements across 40 publications for mammalian sodium channels.
- Comparison of experimental data with theoretical constraints of membrane excitability and resting potential uniqueness.
- Grouping of sodium channels based on excitability properties and comparison with phylogenetic analysis.
Main Results:
- All mammalian sodium channel types, including mutants, adhere to the excitability constraint.
- Muscle-expressed channels generally satisfy the unique resting potential constraint, unlike neuronal channels.
- Excitability properties segregate the nine sodium channels into four distinct groups, aligning with phylogenetic data.
Conclusions:
- Theoretical constraints on membrane excitability and resting potential directly influence sodium channel properties and evolution.
- Functional differences between sodium channel groups can be explained by these constraints.
- The study provides insights into the functional diversification of mammalian voltage-gated sodium channels.
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