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

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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.
Publisher
CAMBRIDGE UNIV PRESS
Issue Date
1998-03
Language
English
Article Type
Article
Keywords

POTASSIUM CHANNEL; DIVALENT-CATIONS; SINOATRIAL NODE; K+ CURRENT; RECTIFICATION; CONDUCTANCE; RECTIFIER; MODULATION; MECHANISM; NEURONS

Citation

JOURNAL OF PHYSIOLOGY-LONDON, v.507, no.3, pp.631 - 638

ISSN
0022-3751
DOI
10.1111/j.1469-7793.1998.631bs.x
URI
http://hdl.handle.net/10203/77791
Appears in Collection
MSE-Journal Papers(저널논문)
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