ISSN:
1432-2013
Keywords:
Key words Ca2+
;
Channel blockade
;
H+
;
HERG channel
;
Potassium channel
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004240050875
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