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Maprotiline block of the human ether-a-go-go-related gene (HERG) K+ channel.
Arch Pharm Res. 2007 Apr; 30(4):453-60.AP

Abstract

Maprotiline, an atypical antidepressant, can induce prolonged QT and torsades de pointes. We studied the effects of maprotiline on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells. Maprotiline induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and tail currents of HERG. The V1/2 values in the absence and presence of 1-20 microM maprotiline were not significantly different, while the values decreased according to the concentrations of the drug at 50-300 microM. The IC50 for a maprotiline block of HERG current in Xenopus oocytes did not change according to depolarization; 39.5 +/- 3.2 microM at -40 mV and 43.6 +/- 2.8 microM at +40 mV. The block of HERG by maprotiline was examined after treatment of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent that neutralizes the positively charged amino-groups of peptide N-terminal and lysine residues. TNBS inhibited the change of V1/2 values induced by 50-300 mM maprotiline, and aggravated the drug-induced gmax decrease. The IC50 for the maprotiline-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 0.13 microM at +20 mV. Our findings suggest that the arrhythmogenic side effects of maprotiline are caused by a blockade of HERG and possibly by a blockade of delayed rectifier K+ channel.

Authors+Show Affiliations

Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon, Korea. shjo@cheju.ac.krNo affiliation info availableNo 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

17489361

Citation

Jo, Su-Hyun, et al. "Maprotiline Block of the Human Ether-a-go-go-related Gene (HERG) K+ Channel." Archives of Pharmacal Research, vol. 30, no. 4, 2007, pp. 453-60.
Jo SH, Hong HK, Jung SJ, et al. Maprotiline block of the human ether-a-go-go-related gene (HERG) K+ channel. Arch Pharm Res. 2007;30(4):453-60.
Jo, S. H., Hong, H. K., Jung, S. J., Chong, S. H., Yun, J. H., Koh, Y. S., & Choe, H. (2007). Maprotiline block of the human ether-a-go-go-related gene (HERG) K+ channel. Archives of Pharmacal Research, 30(4), 453-60.
Jo SH, et al. Maprotiline Block of the Human Ether-a-go-go-related Gene (HERG) K+ Channel. Arch Pharm Res. 2007;30(4):453-60. PubMed PMID: 17489361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maprotiline block of the human ether-a-go-go-related gene (HERG) K+ channel. AU - Jo,Su-Hyun, AU - Hong,Hee-Kyung, AU - Jung,Sung Jun, AU - Chong,Seon Ha, AU - Yun,Ji-Hyun, AU - Koh,Young-Sang, AU - Choe,Han, PY - 2007/5/11/pubmed PY - 2007/5/30/medline PY - 2007/5/11/entrez SP - 453 EP - 60 JF - Archives of pharmacal research JO - Arch Pharm Res VL - 30 IS - 4 N2 - Maprotiline, an atypical antidepressant, can induce prolonged QT and torsades de pointes. We studied the effects of maprotiline on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells. Maprotiline induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and tail currents of HERG. The V1/2 values in the absence and presence of 1-20 microM maprotiline were not significantly different, while the values decreased according to the concentrations of the drug at 50-300 microM. The IC50 for a maprotiline block of HERG current in Xenopus oocytes did not change according to depolarization; 39.5 +/- 3.2 microM at -40 mV and 43.6 +/- 2.8 microM at +40 mV. The block of HERG by maprotiline was examined after treatment of trinitrobenzene sulfonic acid (TNBS), an amino-group reagent that neutralizes the positively charged amino-groups of peptide N-terminal and lysine residues. TNBS inhibited the change of V1/2 values induced by 50-300 mM maprotiline, and aggravated the drug-induced gmax decrease. The IC50 for the maprotiline-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 0.13 microM at +20 mV. Our findings suggest that the arrhythmogenic side effects of maprotiline are caused by a blockade of HERG and possibly by a blockade of delayed rectifier K+ channel. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/17489361/Maprotiline_block_of_the_human_ether_a_go_go_related_gene__HERG__K+_channel_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=17489361.ui DB - PRIME DP - Unbound Medicine ER -