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State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes.
J Physiol. 2000 Jul 15; 526 Pt 2:265-78.JP

Abstract

The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism.

Authors+Show Affiliations

Research Center, Departments of Medicine and Anesthesia, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Canada.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

10896755

Citation

Weerapura, M, et al. "State-dependent Barium Block of Wild-type and Inactivation-deficient HERG Channels in Xenopus Oocytes." The Journal of Physiology, vol. 526 Pt 2, 2000, pp. 265-78.
Weerapura M, Nattel S, Courtemanche M, et al. State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes. J Physiol. 2000;526 Pt 2:265-78.
Weerapura, M., Nattel, S., Courtemanche, M., Doern, D., Ethier, N., & Hebert, T. (2000). State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes. The Journal of Physiology, 526 Pt 2, 265-78.
Weerapura M, et al. State-dependent Barium Block of Wild-type and Inactivation-deficient HERG Channels in Xenopus Oocytes. J Physiol. 2000 Jul 15;526 Pt 2:265-78. PubMed PMID: 10896755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes. AU - Weerapura,M, AU - Nattel,S, AU - Courtemanche,M, AU - Doern,D, AU - Ethier,N, AU - Hebert,T, PY - 2000/7/15/pubmed PY - 2000/9/23/medline PY - 2000/7/15/entrez SP - 265 EP - 78 JF - The Journal of physiology JO - J Physiol VL - 526 Pt 2 N2 - The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/10896755/State_dependent_barium_block_of_wild_type_and_inactivation_deficient_HERG_channels_in_Xenopus_oocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3751&date=2000&volume=526&spage=265 DB - PRIME DP - Unbound Medicine ER -