Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.
Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.
复制标题
DOI：
10.1371/journal.pone.0142730
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jegla T
中科院分区：
文献类型：
--
作者：
Baker EC;Layden MJ;van Rossum DB;Kamel B;Medina M;Simpson E;Jegla T
HCN 通道作为唯一的超极化门控阳离子通道，在两侧对称动物生理学中发挥着独特的作用。它们的电压门控由环核苷酸和磷脂酰肌醇 4,5-二磷酸 (PIP2) 调节。 HCN 通道的激活提供响应超极化的去极化电流，这对于神经元和窦房结的内在节律性至关重要。此外，HCN 通道调节多种神经元的树突兴奋性。关于 HCN 通道的早期功能进化知之甚少，但在基底后生动物门和领鞭毛虫（后生动物的原生动物姐妹群）中存在 HCN 序列，表明该基因家族早于后生动物的出现。我们对来自 Nematostella vectensis（刺胞动物、Anthozoa）的两个 HCN 通道直系同源物进行功能表征，以确定 HCN 通道的哪些特性是在两侧对称动物出现之前建立的。我们发现 Nematostella HCN 通道具有两侧对称动物 HCN 的所有主要功能特征，包括反向电压依赖性、cAMP 和 PIP2 激活以及细胞外 Cs+ 阻断。因此，当电压门控 K+ 通道的功能多样性迅速扩大时，类似两侧对称动物的 HCN 通道已经存在于两侧对称动物和刺胞动物的共同副动物祖先中。 NvHCN1 和 NvHCN2 在浮肿体以及幼年息肉的内胚层和外胚层中广泛表达。
HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa) to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps.