TY - JOUR T1 - Excitability Constraints on Voltage-Gated Sodium Channels A1 - Angelino, Elaine A1 - Brenner, Michael P Y1 - 2007/09/21 N2 - Author SummaryThere are few quantitative examples for how functional constraints bound and shape evolution. Sodium channels are a central player in the propagation of action potentials. Action potentials fire above a critical voltage threshold. Below the voltage threshold the membrane potential recovers to a resting value, which is assumed to be unique. Here we ask whether the properties of mammalian voltage-gated sodium channels are determined by the simplest possible constraints. We demonstrate that the requirements, (1) a voltage threshold and (2) a unique resting potential, severely constrain sodium channel properties. These constraints contain no free parameters, depending only on the concentrations of potassium inside and outside the cell. We test these predictions on functional data from the nine mammalian genes encoding voltage-gated sodium channels. All measurements obey the excitability constraint, whereas channels expressed in the nervous system systematically violate the constraint for a unique resting potential. These properties alone distinguish the nine sodium channels into four groups consistent with phylogenetic analysis. Our calculations suggest that different channel types have evolved to perform different tasks. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 3 IS - 9 UR - https://doi.org/10.1371/journal.pcbi.0030177 SP - e177 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0030177 ER -