A family of hyperpolarization-activated mammalian cation channels
A family of hyperpolarization-activated mammalian cation channels
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作者：
Ludwig, A;Zong, XG;Biel, M
自发兴奋的神经元(1-3)和心脏细胞(4-6)的起搏活动受去极化的混合Na+/K+电流控制，称为i-h(或心脏窦房结中的i-f)(1，4)。该电流在质膜超极化时被激活。除使起搏细胞去极化外，i-h还参与确定神经元的静息膜电位(1，2)，并提供一种机制来限制这些细胞的超极化电流(7-9)。诱导环AMP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I-h，该机制涉及环核苷酸与介导I-h的通道的直接结合(10-13)。在这里，我们报道了编码超极化激活阳离子通道(HAC1)的基因的分子克隆和功能表达，该通道存在于大脑和心脏中。该通道表现出i-h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，它们在大脑中特异表达，表明存在一类超极化激活的阳离子通道。
Pacemaker activity of spontaneously active neurons(1-3) and heart cells(4-6) is controlled by a depolarizing, mixed Na+/K+ current, named I-h (or I-f in the sinoatrial node of the heart)(1,4). This current is activated on hyperpolarization of the plasma membrane. In addition to depolarizing pacemaker cells, I-h is involved in determining the resting membrane potential of neurons(1,2) and provides a mechanism to limit hyperpolarizing currents in these cells(7-9). Hormones and neurotransmitters that induce a rise in cyclic AMP levels increase I-h by a mechanism that is independent of protein phosphorylation, and which involves direct binding of the cyclic nucleotide to the channel that mediates I-h(10-13). 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 I-h 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.