Kase Daisuke, Imoto Keiji
Department of Information Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8787, Japan.
J Signal Transduct. 2012;2012:619747. doi: 10.1155/2012/619747. Epub 2012 Aug 13.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP(2), and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.
超极化激活的环核苷酸门控(HCN)通道最初是在心脏细胞中被报道的,最近发现其在健康和患病大脑的多种神经功能中发挥作用。当膜电位超极化时,HCN通道会产生内向电流。HCN通道的电压依赖性受细胞内信号级联反应调节,该反应包含环磷酸腺苷、磷脂酰肌醇-4,5-二磷酸(PIP₂)和TRIP8b。此外,电压门控钾通道对HCN通道活性有强烈影响。由于这些有趣的特性,HCN通道电流(以前称为趣电流)可以具有由调节因子的微妙平衡所决定的广泛功能。这些多方面的特性也使得预测和阐明HCN通道在实际神经元中的功能作用变得困难。在本文中,我们关注HCN通道对神经活动的影响。将总结先前报道的HCN通道的功能,并通过简化模型神经元的数值模拟来解释其机制。