Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties.
Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties.
复制标题
HCN通道的电压依赖性磁滞：两种模式之间的转换会影响起搏器特性。
DOI：
10.1085/jgp.200409130
复制
发表时间：
2005-03
影响因子：
3.8
通讯作者：
Elinder, Fredrik
中科院分区：
文献类型：
--
作者：
Mannikko, Roope;Pandey, Shilpi;Larsson, H Peter;Elinder, Fredrik
超极化激活的环核苷酸门控（HCN）离子通道对于大脑和心脏中的节律性活动是重要的。在这项研究中，使用离子和门控电流的测量，我们表明，克隆的sphHCN通道在正常门控过程中的电压依赖性经历了一个滞后。例如，与去极化保持电位相比，当从超极化保持电位测量时，门控电荷对电压曲线Q（V）和电导对电压曲线G（V）都偏移约+60 mV。此外，尾电流和激活电流的动力学与Q（V）和G（V）曲线的电压偏移平行地变化。哺乳动物HCN 1通道在其离子电流中显示出类似的效应，表明哺乳动物HCN通道也经历电压滞后。我们提出了一个模型，其中HCN通道在两种模式之间的过渡。两种模式中的电压依赖性相对于彼此移位，并且两种模式的占用取决于通道的先前激活。电压依赖性的变化很快（τ <100 ms），并且不伴有任何明显的失活。在HCN 1通道中，与1 mM K溶液相比，100 mM K细胞外溶液中电压依赖性的偏移较慢。基于这些研究结果，我们认为，分子构象类似于缓慢（C型）失活的K通道的电压滞后HCN通道的基础。电压滞后导致HCN通道在起搏器周期的不同阶段显示不同的电压依赖性。计算机模拟表明，HCN通道的电压滞后降低了起搏细胞心律失常的风险。
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels are important for rhythmic activity in the brain and in the heart. In this study, using ionic and gating current measurements, we show that cloned spHCN channels undergo a hysteresis in their voltage dependence during normal gating. For example, both the gating charge versus voltage curve, Q(V), and the conductance versus voltage curve, G(V), are shifted by about +60 mV when measured from a hyperpolarized holding potential compared with a depolarized holding potential. In addition, the kinetics of the tail current and the activation current change in parallel to the voltage shifts of the Q(V) and G(V) curves. Mammalian HCN1 channels display similar effects in their ionic currents, suggesting that the mammalian HCN channels also undergo voltage hysteresis. We propose a model in which HCN channels transit between two modes. The voltage dependence in the two modes is shifted relative to each other, and the occupancy of the two modes depends on the previous activation of the channel. The shifts in the voltage dependence are fast (τ ≈ 100 ms) and are not accompanied by any apparent inactivation. In HCN1 channels, the shift in voltage dependence is slower in a 100 mM K extracellular solution compared with a 1 mM K solution. Based on these findings, we suggest that molecular conformations similar to slow (C-type) inactivation of K channels underlie voltage hysteresis in HCN channels. The voltage hysteresis results in HCN channels displaying different voltage dependences during different phases in the pacemaker cycle. Computer simulations suggest that voltage hysteresis in HCN channels decreases the risk of arrhythmia in pacemaker cells.