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Blockade of HERG channels expressed in Xenopus oocytes by external H+.
Pflugers Arch. 1999 Jun; 438(1):23-9.PA

Abstract

We have investigated the effect of external H+ concentration ([H+]o) on the human-ether-a-go-go-related gene (HERG) current (IHERG), the molecular equivalent of the cardiac delayed rectifier potassium current (IKr), expressed in Xenopus oocytes, using the two-microelectrode voltage-clamp technique. When [H+]o was increased, the amplitude of the IHERG 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, V1/2, 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 (gmax) 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 V1/2 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 gmax 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 V1/2) and the decrease in gmax. With respect to the voltage-dependent blockade, the interaction between H+ and Ca2+ is competitive, whereas for the decreasing gmax, their interaction is non-competitive.

Authors+Show Affiliations

Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10370083

Citation

Jo, S H., et al. "Blockade of HERG Channels Expressed in Xenopus Oocytes By External H+." Pflugers Archiv : European Journal of Physiology, vol. 438, no. 1, 1999, pp. 23-9.
Jo SH, Youm JB, Kim I, et al. Blockade of HERG channels expressed in Xenopus oocytes by external H+. Pflugers Arch. 1999;438(1):23-9.
Jo, S. H., Youm, J. B., Kim, I., Lee, C. O., Earm, Y. E., & Ho, W. K. (1999). Blockade of HERG channels expressed in Xenopus oocytes by external H+. Pflugers Archiv : European Journal of Physiology, 438(1), 23-9.
Jo SH, et al. Blockade of HERG Channels Expressed in Xenopus Oocytes By External H+. Pflugers Arch. 1999;438(1):23-9. PubMed PMID: 10370083.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of HERG channels expressed in Xenopus oocytes by external H+. AU - Jo,S H, AU - Youm,J B, AU - Kim,I, AU - Lee,C O, AU - Earm,Y E, AU - Ho,W K, PY - 1999/6/17/pubmed PY - 1999/6/17/medline PY - 1999/6/17/entrez SP - 23 EP - 9 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 438 IS - 1 N2 - We have investigated the effect of external H+ concentration ([H+]o) on the human-ether-a-go-go-related gene (HERG) current (IHERG), the molecular equivalent of the cardiac delayed rectifier potassium current (IKr), expressed in Xenopus oocytes, using the two-microelectrode voltage-clamp technique. When [H+]o was increased, the amplitude of the IHERG 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, V1/2, 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 (gmax) 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 V1/2 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 gmax 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 V1/2) and the decrease in gmax. With respect to the voltage-dependent blockade, the interaction between H+ and Ca2+ is competitive, whereas for the decreasing gmax, their interaction is non-competitive. SN - 0031-6768 UR - https://www.unboundmedicine.com/medline/citation/10370083/Blockade_of_HERG_channels_expressed_in_Xenopus_oocytes_by_external_H+_ L2 - https://dx.doi.org/10.1007/s004240050875 DB - PRIME DP - Unbound Medicine ER -