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Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels.
J Cardiovasc Pharmacol. 2006 Jan; 47(1):21-9.JC

Abstract

Berberine prolongs the duration of cardiac action potentials without affecting resting membrane potential or action potential amplitude. Controversy exists regarding whether berberine exerts this action by preferential block of different components of the delayed rectifying potassium current, I(Kr) and I(Ks). Here we have studied the effects of berberine on hERG (I(Kr)) and KCNQ1/KCNE1 (I(Ks)) channels expressed in HEK-293 cells and Xenopus oocytes. In HEK-293 cells, the IC50 for berberine was 3.1 +/- 0.5 microM on hERG compared with 11 +/- 4% decreases on KCNQ1/KCNE1 channels by 100 microM berberine. Likewise in oocytes, hERG channels were more sensitive to block by berberine (IC50 = 80 +/- 5 microM) compared with KCNQ1/KCNE1 channels (approximately 20% block at 300 microM). hERG block was markedly increased by membrane depolarization. Mutation to Ala of Y652 or F656 located on the S6 domain, or V625 located at the base of the pore helix of hERG decreased sensitivity to block by berberine. An inactivation-deficient mutant hERG channel (G628C/S631C) was also blocked by berberine. Together these findings indicate that berberine preferentially blocks the open state of hERG channels by interacting with specific residues that were previously reported to be important for binding of more potent antagonists.

Authors+Show Affiliations

Unidad Carlos Mendez del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Mexico.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

16424781

Citation

Rodriguez-Menchaca, Aldo, et al. "Block of HERG Channels By Berberine: Mechanisms of Voltage- and State-dependence Probed With Site-directed Mutant Channels." Journal of Cardiovascular Pharmacology, vol. 47, no. 1, 2006, pp. 21-9.
Rodriguez-Menchaca A, Ferrer-Villada T, Lara J, et al. Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. J Cardiovasc Pharmacol. 2006;47(1):21-9.
Rodriguez-Menchaca, A., Ferrer-Villada, T., Lara, J., Fernandez, D., Navarro-Polanco, R. A., & Sanchez-Chapula, J. A. (2006). Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. Journal of Cardiovascular Pharmacology, 47(1), 21-9.
Rodriguez-Menchaca A, et al. Block of HERG Channels By Berberine: Mechanisms of Voltage- and State-dependence Probed With Site-directed Mutant Channels. J Cardiovasc Pharmacol. 2006;47(1):21-9. PubMed PMID: 16424781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Block of HERG channels by berberine: mechanisms of voltage- and state-dependence probed with site-directed mutant channels. AU - Rodriguez-Menchaca,Aldo, AU - Ferrer-Villada,Tania, AU - Lara,Jesus, AU - Fernandez,David, AU - Navarro-Polanco,Ricardo A, AU - Sanchez-Chapula,Jose A, PY - 2006/1/21/pubmed PY - 2006/5/23/medline PY - 2006/1/21/entrez SP - 21 EP - 9 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 47 IS - 1 N2 - Berberine prolongs the duration of cardiac action potentials without affecting resting membrane potential or action potential amplitude. Controversy exists regarding whether berberine exerts this action by preferential block of different components of the delayed rectifying potassium current, I(Kr) and I(Ks). Here we have studied the effects of berberine on hERG (I(Kr)) and KCNQ1/KCNE1 (I(Ks)) channels expressed in HEK-293 cells and Xenopus oocytes. In HEK-293 cells, the IC50 for berberine was 3.1 +/- 0.5 microM on hERG compared with 11 +/- 4% decreases on KCNQ1/KCNE1 channels by 100 microM berberine. Likewise in oocytes, hERG channels were more sensitive to block by berberine (IC50 = 80 +/- 5 microM) compared with KCNQ1/KCNE1 channels (approximately 20% block at 300 microM). hERG block was markedly increased by membrane depolarization. Mutation to Ala of Y652 or F656 located on the S6 domain, or V625 located at the base of the pore helix of hERG decreased sensitivity to block by berberine. An inactivation-deficient mutant hERG channel (G628C/S631C) was also blocked by berberine. Together these findings indicate that berberine preferentially blocks the open state of hERG channels by interacting with specific residues that were previously reported to be important for binding of more potent antagonists. SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/16424781/Block_of_HERG_channels_by_berberine:_mechanisms_of_voltage__and_state_dependence_probed_with_site_directed_mutant_channels_ L2 - https://doi.org/10.1097/01.fjc.0000191564.52242.00 DB - PRIME DP - Unbound Medicine ER -