Excitability constraints on voltage-gated sodium channels.
Excitability constraints on voltage-gated sodium channels.
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DOI：
10.1371/journal.pcbi.0030177
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发表时间：
2007-09
影响因子：
4.3
通讯作者：
Brenner, Michael P.
中科院分区：
文献类型：
--
作者：
Angelino, Elaine;Brenner, Michael P.
我们通过对哺乳动物电压门控钠通道的分析来研究功能限制如何约束和塑造进化。钠通道的主要功能是允许动作电位的传播。自霍奇金和赫胥黎以来，数学模型表明，钠通道的特性需要受到严格约束，动作电位才能传播。哺乳动物有九个编码电压门控钠通道的基因，其中许多基因在序列上有超过约90%的同一性。这种序列相似性大概对应着功能的相似性，这与这些特性必须受到严格约束的观点是一致的。然而，编码钠通道的基因的多样性提出了一个问题：为什么会有这么多？我们证明，限制钠通道多样性的最简单的理论约束——膜兴奋性的要求和静息电位的唯一性——直接作用于约束钠通道的特性。我们将预测的约束与从文献中收集的哺乳动物钠通道特性的功能数据进行比较，包括来自40篇出版物的172组不同的测量数据，有野生型的也有突变型的，且是在各种条件下的。来自所有通道类型（包括突变体）的数据都符合兴奋性约束；另一方面，在肌肉中表达的通道往往符合独特静息电位的约束，而在神经组织中表达的通道则不符合。仅兴奋性特性就将九个钠通道区分为四个不同的组，这与系统发育分析是一致的。我们的计算为这些组之间的功能差异提供了解释。
关于功能限制如何约束和塑造进化，定量的例子很少。钠通道在动作电位的传播中起着核心作用。动作电位在一个临界电压阈值之上激发。在电压阈值之下，膜电位恢复到一个静息值，这个静息值被假定是唯一的。在这里我们要问的是，哺乳动物电压门控钠通道的特性是否由最简单的可能约束所决定。我们证明，（1）一个电压阈值和（2）一个独特的静息电位这两个要求严重约束了钠通道的特性。这些约束不包含自由参数，仅取决于细胞内外钾离子的浓度。我们用来自编码电压门控钠通道的九个哺乳动物基因的功能数据来检验这些预测。所有的测量都符合兴奋性约束，而在神经系统中表达的通道有系统地违反独特静息电位的约束。仅这些特性就将九个钠通道区分为四个组，这与系统发育分析是一致的。我们的计算表明，不同的通道类型已经进化到执行不同的任务。
We study how functional constraints bound and shape evolution through an analysis of mammalian voltage-gated sodium channels. The primary function of sodium channels is to allow the propagation of action potentials. Since Hodgkin and Huxley, mathematical models have suggested that sodium channel properties need to be tightly constrained for an action potential to propagate. There are nine mammalian genes encoding voltage-gated sodium channels, many of which are more than ≈90% identical by sequence. This sequence similarity presumably corresponds to similarity of function, consistent with the idea that these properties must be tightly constrained. However, the multiplicity of genes encoding sodium channels raises the question: why are there so many? We demonstrate that the simplest theoretical constraints bounding sodium channel diversity—the requirements of membrane excitability and the uniqueness of the resting potential—act directly on constraining sodium channel properties. We compare the predicted constraints with functional data on mammalian sodium channel properties collected from the literature, including 172 different sets of measurements from 40 publications, wild-type and mutant, under a variety of conditions. The data from all channel types, including mutants, obeys the excitability constraint; on the other hand, channels expressed in muscle tend to obey the constraint of a unique resting potential, while channels expressed in neuronal tissue do not. The excitability properties alone distinguish the nine sodium channels into four different groups that are consistent with phylogenetic analysis. Our calculations suggest interpretations for the functional differences between these groups. There 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.
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影响因子：
64.8
作者：
Dekel, E;Alon, U
通讯作者：
Alon, U
影响因子：
5.5
作者：
Baker, MD;Chandra, SY;Wood, JN
通讯作者：
Wood, JN
DOI：
10.1016/s0169-328x(02)00188-2
发表时间：
2002-06-30
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Burbidge, SA;Dale, TJ;Clare, JJ
通讯作者：
Clare, JJ
影响因子：
16.2
作者：
Lossin, C;Wang, DW;George, AL
通讯作者：
George, AL
影响因子：
3.3
作者：
McCormack, DA;Lim, KF
通讯作者：
Lim, KF