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Blockade of HERG channels expressed in Xenopus oocytes by external H+

Content Provider	Springer Nature Link
Author	Jo, Su Hyun Youm, Jae Boum Kim, Injune Lee, Chin O. Earm, Yung E. Ho, Won Kyung
Copyright Year	1999
Abstract	We have investigated the effect of external H+ concentration ([H+]o)on the human-ether-a-go-go-related gene (HERG) current (I HERG), the molecular equivalent of the cardiac delayed rectifier potassium current (I Kr), expressed in Xenopus oocytes, using the two-microelectrode voltage-clamp technique. When [H+]o was increased, the amplitude of the I HERG elicited by depolarization decreased, and the rate of current decay on repolarization was accelerated. The activation curve shifted to a more positive potential at lower external pH (pHo) values (the potential required for half-maximum activation, V 1/2, was: –41.8 mV, –38.0 mV, –33.7 mV, –26.7 mV in pHo 8.0, 7.0, 6.6, 6.2, respectively). The maximum conductance (g max) was also affected by [H+]o: a reduction of 7.9%, 14.6%, and 22.8% was effected by decreasing pHo from 8.0 to 7.0, 6.6, and 6.2, respectively. We then tested whether this pH effect was affected by the external Ca2+ concentration, which is also known to block HERG channels. When the extracellular Ca2+ concentration was increased from 0.5 mM to 5 mM, the shift in V 1/2 caused by increasing [H+]o was attenuated, suggesting that these two ions compete for the same binding site. On the other hand, the decrease in g max caused by increasing [H+]o was not significantly affected by changing external Ca2+ levels. The results indicate that HERG channels are inhibited by [H+]o by two different mechanisms: voltage-dependent blockade (shift of V 1/2) and the decrease in g max. With respect to the voltage-dependent blockade, the interaction between H+ and Ca2+ is competitive, whereas for the decreasing g max, their interaction is non-competitive.
Starting Page	23
Ending Page	29
Page Count	7
File Format	PDF
ISSN	00316768
Journal	Pflügers Archiv
Volume Number	438
Issue Number	1
e-ISSN	14322013
Language	English
Publisher	Springer-Verlag
Publisher Date	1999-05-17
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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