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Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel.
Life Sci. 2008 Jan 30; 82(5-6):331-40.LS

Abstract

Protriptyline, a tricyclic antidepressant for psychiatric disorders, can induce prolonged QT, torsades de pointes, and sudden death. We studied the effects of protriptyline on human ether-à-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells. Protriptyline induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and HERG tail currents. The IC(50) for protriptyline block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 142.0 microM at -40 mV to 91.7 microM at 0 mV to 52.9 microM at +40 mV. The voltage dependence of the block could be fit with a monoexponential function, and the fractional electrical distance was estimated to be delta=0.93. The IC(50) for the protriptyline-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 1.18 microM at +20 mV. Protriptyline affected channels in the activated and inactivated states, but not in the closed states. HERG blockade by protriptyline was use-dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation. Our findings suggest that inhibition of HERG currents may contribute to the arrhythmogenic side effects of protriptyline.

Authors+Show Affiliations

Department of Physiology, Institute of Bioscience and Biotechnology, Kangwon National University College of Medicine, Chuncheon 200-701, South Korea. suhyunjo@kangwon.ac.krNo 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

18191158

Citation

Jo, Su-Hyun, et al. "Protriptyline Block of the Human Ether-à-go-go-related Gene (HERG) K+ Channel." Life Sciences, vol. 82, no. 5-6, 2008, pp. 331-40.
Jo SH, Hong HK, Chong SH, et al. Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel. Life Sci. 2008;82(5-6):331-40.
Jo, S. H., Hong, H. K., Chong, S. H., & Choe, H. (2008). Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel. Life Sciences, 82(5-6), 331-40. https://doi.org/10.1016/j.lfs.2007.12.004
Jo SH, et al. Protriptyline Block of the Human Ether-à-go-go-related Gene (HERG) K+ Channel. Life Sci. 2008 Jan 30;82(5-6):331-40. PubMed PMID: 18191158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protriptyline block of the human ether-à-go-go-related gene (HERG) K+ channel. AU - Jo,Su-Hyun, AU - Hong,Hee-Kyung, AU - Chong,Seon Ha, AU - Choe,Han, Y1 - 2008/01/11/ PY - 2007/07/20/received PY - 2007/11/30/revised PY - 2007/12/04/accepted PY - 2008/1/15/pubmed PY - 2008/3/14/medline PY - 2008/1/15/entrez SP - 331 EP - 40 JF - Life sciences JO - Life Sci VL - 82 IS - 5-6 N2 - Protriptyline, a tricyclic antidepressant for psychiatric disorders, can induce prolonged QT, torsades de pointes, and sudden death. We studied the effects of protriptyline on human ether-à-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells. Protriptyline induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and HERG tail currents. The IC(50) for protriptyline block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 142.0 microM at -40 mV to 91.7 microM at 0 mV to 52.9 microM at +40 mV. The voltage dependence of the block could be fit with a monoexponential function, and the fractional electrical distance was estimated to be delta=0.93. The IC(50) for the protriptyline-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 1.18 microM at +20 mV. Protriptyline affected channels in the activated and inactivated states, but not in the closed states. HERG blockade by protriptyline was use-dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation. Our findings suggest that inhibition of HERG currents may contribute to the arrhythmogenic side effects of protriptyline. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/18191158/Protriptyline_block_of_the_human_ether_��_go_go_related_gene__HERG__K+_channel_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(07)00873-9 DB - PRIME DP - Unbound Medicine ER -