Kinetic and ionic properties of the human HCN2 pacemaker channel

Kinetic and ionic properties of the human HCN2 pacemaker channel
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人类 HCN2 起搏器通道的动力学和离子特性

DOI:
10.1007/s004249900225
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发表时间:
2000
期刊:
Pflügers Archiv
影响因子:
--
通讯作者:
D. DiFrancesco
D. DiFrancesco
中科院分区:
--
文献类型:
--
作者:
A. Moroni;A. Barbuti;C. Altomare;C. Viscomi;Julie Morgan;M. Baruscotti;D. DiFrancesco

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抽象的。编码超极化激活的“起搏器”通道 HCN2 的人类 cDNA 在 Phoenix 细胞中表达,并产生超极化时激活的内向电流 (IhHCN2)。 IhHCN2 平均在 –83.1 mV 处半激活,其动力学可以通过二阶 Hodgkin-Huxley 门控来描述。时间常数曲线呈钟形,峰值位于 –82.2 mV。使用 115 mM 外部 Na+ 和 30 mM 外部 K+ 时,IhHCN2 在 –17.1 mV 处反转,平均电导为 5.6 nS。降低外部 K+ 或 Na+ 浓度会导致 IhHCN2 电导浓度依赖性降低,并导致反转电位发生超极化转变。根据 Woodhull 型阻断模型,外部 Cs+ 离子 (5 mM) 以电压依赖性方式阻断 IhHCN2,距外膜表面的电距离为 0.66,0 mV 下的解离常数为 15 mM。使用毛喉素增加细胞质 cAMP,通过将电流激活曲线移动到更正的电压 (11.7 mV) 来增加 IhHCN2。将由内而外的大片的细胞内侧暴露于 cAMP 会导致通道开放概率曲线发生去极化偏移(10 µM cAMP 时为 15.2 mV)。这些结果表明,虽然 hHCN2 通道与天然心脏 f 通道具有一些相同的特性,但在渗透性和阻断特性方面也存在差异,这表明天然通道可能不是简单地由同聚结构组成。
Abstract. Human cDNA coding for the hyperpolarization-activated "pacemaker" channel HCN2 was expressed in Phoenix cells and yielded an inward current (IhHCN2) activated on hyperpolarization. The average IhHCN2 was half-activated at –83.1 mV and its kinetics could be described by second-order Hodgkin–Huxley gating. The time constant curve was bell-shaped and peaked at –82.2 mV. With 115 mM external Na+ and 30 mM external K+, IhHCN2 reversed at –17.1 mV, and had a mean conductance of 5.6 nS. Reducing the external K+ or Na+ concentration led to a concentration-dependent reduction of the IhHCN2 conductance and to a hyperpolarizing shift of reversal potential. External Cs+ ions (5 mM) blocked IhHCN2 in a voltage-dependent way according to a Woodhull-type block model, at an electrical distance of 0.66 from the external membrane surface, and with a dissociation constant of 15 mM at 0 mV. Increasing cytoplasmic cAMP using forskolin increased IhHCN2 by shifting the current activation curve to more positive voltages (11.7 mV). Exposure of the intracellular side of inside-out macro-patches to cAMP led to a depolarizing shift of the channel open probability curve (15.2 mV with 10 µM cAMP). These results indicate that although hHCN2 channels share several properties with native cardiac f-channels, differences also exist in permeability and block properties, suggesting that native channels may not be composed simply of homomeric constructs.
DOI: 10.1089/hum.1996.7.12-1405
发表时间: 1996-08-01
期刊: HUMAN GENE THERAPY
影响因子: 4.2
作者:
Kinsella, TM;Nolan, GP
通讯作者: Nolan, GP
成年犬心室肌细胞中的起搏器电流 i(f)。
DOI: 10.1113/jphysiol.1995.sp020743
发表时间: 1995
期刊: The Journal of physiology
影响因子: --
作者:
Yu,H;Chang,F;Cohen,IS
通讯作者: Cohen,IS