Voltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+

被引:40
作者
Ho, WK
Kim, I
Lee, CO
Earm, YE
机构
[1] Seoul Natl Univ, Coll Med, Dept Physiol, Seoul 110799, South Korea
[2] Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1998年 / 507卷 / 03期
关键词
D O I
10.1111/j.1469-7793.1998.631bs.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. We expressed the human eag-related gene (HERG), which is known to encode the delayed rectifier K+ current (I-Kr) in cardiac muscle, in Xenopus oocytes. Using a two-microelectrode voltage clamp technique, the effect of external Ca2+ and Mg2+ on the HERG current (I-HERG) was investigated. 2. When [Ca2+](o) was increased, the amplitude of outward I-HERG elicited by depolarization decreased, and the rate of current onset slowed. The rate of current decay observed on repolarization was greatly accelerated. The threshold and fully activated potential of I-HERG shifted to a more positive potential. On the other hand, the inactivation property represented by the negative slope of the I-V curve and the instantaneous conductance of I-HERG were little affected by [Ca2+](o). 3. The effect of [Ca2+](o) on I-HERG can be interpreted using the channel blockade model. The blockade is voltage dependent; smaller dissociation constants (K-M) at more negative potentials indicate that block is facilitated by hyperpolarization. K-M changes e-fold for 14.5 mV and the fractional electrical distance of the binding site calculated from this value is 0.86. 4. Blockade by a low concentration of Ca2+ (0.5 mM) was inhibited by increasing [K+](o) (from 2 to 20 mM), whereas blockade by a high concentration of Ca2+ (5 mM) was not affected by varying [K+](o), indicating that there is competition between permeating ions and blocking ions. 5. The effect of [Mg2+](o) on I-HERG was qualitatively similar to that of [Ca2+](o), but the potency was lower. 6. These results suggest that external Ca2+ and Mg2+ block the HERG channel in a voltage-and time-dependent manner, resulting in a voltage dependence which has been regarded as a property of the activation gate.
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页码:631 / 638
页数:8
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