Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M
Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany.
Nature. 1998 Jun 11;393(6685):587-91. doi: 10.1038/31255.
Pacemaker activity of spontaneously active neurons and heart cells is controlled by a depolarizing, mixed Na+/K+ current, named Ih (or I(f) in the sinoatrial node of the heart). This current is activated on hyperpolarization of the plasma membrane. In addition to depolarizing pacemaker cells, Ih is involved in determining the resting membrane potential of neurons and provides a mechanism to limit hyperpolarizing currents in these cells. Hormones and neurotransmitters that induce a rise in cyclic AMP levels increase Ih by a mechanism that is independent of protein phosphorylation, and which involves direct binding of the cyclic nucleotide to the channel that mediates Ih. Here we report the molecular cloning and functional expression of the gene encoding a hyperpolarization-activated cation channel (HAC1) that is present in brain and heart. This channel exhibits the general properties of Ih channels. We have also identified full-length sequences of two related channels, HAC2 and HAC3, that are specifically expressed in the brain, indicating the existence of a family of hyperpolarization-activated cation channels.
自发活动神经元和心脏细胞的起搏活动受一种去极化的混合Na⁺/K⁺电流控制，该电流称为Ih（在心脏窦房结中为I(f)）。这种电流在质膜超极化时被激活。除了使起搏细胞去极化外，Ih还参与确定神经元的静息膜电位，并提供一种机制来限制这些细胞中的超极化电流。诱导环磷酸腺苷（cAMP）水平升高的激素和神经递质通过一种独立于蛋白质磷酸化的机制增加Ih，该机制涉及环核苷酸直接与介导Ih的通道结合。在此，我们报告了编码一种存在于脑和心脏中的超极化激活阳离子通道（HAC1）的基因的分子克隆和功能表达。该通道具有Ih通道的一般特性。我们还鉴定了两个相关通道HAC2和HAC3的全长序列，它们在脑中特异性表达，表明存在一个超极化激活阳离子通道家族。
