Li H.a· Geng D.b,c· Zheng R.b,c· Wang R.b,c· Li Y.b,c· Liu Y.d· Jia Q.e· Zhang F.b,c

Author affiliations

aDepartment of Orthopaedic Surgery, Institute of Biomechanical Science and Biomechanical Key Laboratory of Hebei Province, Third Hospital of Hebei Medical University, Shijiazhuang, China
bThe Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China
cDepartment of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China
dThe Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science and Technology, Shijiazhuang, China
eDepartment of Pharmocology, Hebei Medical University, Shijiazhuang, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Received: March 25, 2022
Accepted: October 05, 2022
Published online: December 14, 2022

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

Introduction: Voltage-gated Kv7/M potassium channels play an essential role in the control of membrane potential and neuronal excitability. Fangchinoline, a bisbenzylisoquinoline alkaloid, displays extensive biological activities including antitumor, anti-inflammatory, and antihypertension effects. In this study, we investigated the effects of fangchinoline on Kv7/M channels. Methods: A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from mouse dorsal root ganglion (DRG) neurons. Results: Fangchinoline inhibited Kv7.2/Kv7.3 currents in a concentration-dependent manner, with an IC50 of 9.5 ± 1.2 μM. Fangchinoline significantly inhibited Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.3/Kv7.5 channels without selective effects. Furthermore, fangchinoline significantly slowed the activation of Kv7.1-Kv7.5 channels and inhibited native M-channel currents of DRG neurons. Conclusion: Taken together, our findings indicate that fangchinoline concentration-dependently inhibited Kv7/M channel currents.

© 2022 S. Karger AG, Basel

References Fan B, Zhang X, Ma Y, Zhang A. Fangchinoline induces apoptosis, autophagy and energetic impairment in bladder cancer. Cell Physiol Biochem. 2017;43(3):1003–11. Zhou L, Hong G, Li S, Liu Q, Song F, Zhao J, et al. Fangchinoline protects against bone loss in OVX mice via inhibiting osteoclast formation, bone resorption and RANKL-induced signaling. Int J Biol Sci. 2020;16(2):309–19. Li T, Xu XH, Guo X, Yuan T, Tang ZH, Jiang XM, et al. Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus. Biochem Pharmacol. 2020 May;175:113921. Wu Q, Liu H, Zhou M. Fangchinoline ameliorates diabetic retinopathy by inhibiting receptor for advanced glycation end-products (RAGE)-Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in streptozotocin (STZ)-Induced diabetic rats. Med Sci Monit. 2019 Feb 11;25:1113–21. Bao F, Tao L, Zhang H. Neuroprotective effect of natural alkaloid fangchinoline against oxidative glutamate toxicity: involvement of keap1-nrf2 Axis regulation. Cell Mol Neurobiol. 2019 Nov;39(8):1177–86. Shine VJ, Latha PG, Suja SNR, Anuja GI, Raj G, Rajasekharan SN. Ameliorative effect of alkaloid extract of cyclea peltata (poir.) Hook. f. & Thoms. roots (ACP) on APAP/CCl4 induced liver toxicity in wistar rats and in vitro free radical scavenging property. Asian Pac J Trop Biomed. 2014 Feb;4(2):143–51. Kong XP, Ren HQ, Liu EYL, Leung KW, Guo SC, Duan R, et al. The cholinesterase inhibitory properties of stephaniae tetrandrae radix. Molecules. 2020 Dec 14;25(24):5914. Li C, Lu Q, Huang P, Fu T, Li C, Guo L, et al. Activity-dependent downregulation of M-Type (Kv7) K(+) channels surface expression requires the activation of iGluRs/Ca(2+)/PKC signaling pathway in hippocampal neuron. Neuropharmacology. 2015 Aug;95:154–67. Ling J, Erol F, Gu JG. Role of KCNQ2 channels in orofacial cold sensitivity: KCNQ2 upregulation in trigeminal ganglion neurons after infraorbital nerve chronic constrictive injury. Neurosci Lett. 2018 Jan 18;664:84–90. Zhang H, Liu Y, Xu J, Zhang F, Liang H, Du X, et al. Membrane microdomain determines the specificity of receptor-mediated modulation of Kv7/M potassium currents. Neuroscience. 2013 Dec 19;254:70–9. Jones RT, Faas GC, Mody I. Intracellular bicarbonate regulates action potential generation via KCNQ channel modulation. J Neurosci. 2014 Mar 19;34(12):4409–17. Vicente-Baz J, Lopez-Garcia JA, Rivera-Arconada I. Effects of novel subtype selective M-current activators on spinal reflexes in vitro: comparison with retigabine. Neuropharmacology. 2016 Oct;109:131–8. Kim YS, Nibbelink DW, Overall JE. Factor structure and reliability of the Alzheimer’s disease assessment scale in a multicenter trial with linopirdine. J Geriatr Psychiatry Neurol. 1994 Apr–Jun;7(2):74–83. Greene DL, Kang S, Hoshi N. XE991 and linopirdine are state-dependent inhibitors for Kv7/KCNQ channels that favor activated single subunits. J Pharmacol Exp Ther. 2017 Jul;362(1):177–85. Zhang F, Mi Y, Qi JL, Li JW, Si M, Guan BC, et al. Modulation of K(v)7 potassium channels by a novel opener pyrazolo[1, 5-a]pyrimidin-7(4H)-one compound QO-58. Br J Pharmacol. 2013 Feb;168(4):1030–42. Zhang F, Liu Y, Tang F, Liang B, Chen H, Zhang H, et al. Electrophysiological and pharmacological characterization of a novel and potent neuronal Kv7 channel opener SCR2682 for antiepilepsy. FASEB J. 2019 Aug;33(8):9154–66. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. J Pharmacol Pharmacother. 2010 Jul;1(2):94–9. McGrath EE, Blades Z, Anderson PB. Chylothorax: aetiology, diagnosis and therapeutic options. Respir Med. 2010 Jan;104(1):1–8. Lee SH, Kang J, Ho A, Watanabe H, Bolshakov VY, Shen J. APP family regulates neuronal excitability and synaptic plasticity but not neuronal survival. Neuron. 2020 Nov 25;108(4):676–90.e8. Rockwood K, Stolee P. Responsiveness of outcome measures used in an antidementia drug trial. Alzheimer Dis Assoc Disord. 2000 Jul–Sep;14(3):182–5. Goodwill AG, Fu L, Noblet JN, Casalini ED, Sassoon D, Berwick ZC, et al. KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine. Am J Physiol Heart Circ Physiol. 2016 Mar 15;310(6):H693–704. Hedegaard ER, Johnsen J, Povlsen JA, Jespersen NR, Shanmuganathan JA, Laursen MR, et al. Inhibition of KV7 channels protects the rat heart against myocardial ischemia and reperfusion injury. J Pharmacol Exp Ther. 2016 Apr;357(1):94–102. Zaczek R, Chorvat RJ, Saye JA, Pierdomenico ME, Maciag CM, Logue AR, et al. Two new potent neurotransmitter release enhancers, 10, 10-bis (4-pyridinylmethyl)-9 (10H)-anthracenone and 10, 10-bis (2-fluoro-4-pyridinylmethyl)-9 (10H)-anthracenone: comparison to linopirdine. J Pharmacol Exp Ther. 1998 May;285(2):724–30. Trompoukis G, Rigas P, Leontiadis LJ, Papatheodoropoulos C. Ih, GIRK, and KCNQ/Kv7 channels differently modulate sharp wave: ripples in the dorsal and ventral hippocampus. Mol Cell Neurosci. 2020 Sep;107:103531. Hu HN, Zhou PZ, Chen F, Li M, Nan FJ, Gao ZB. Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels. Acta Pharmacol Sin. 2013 Oct;34(10):1359–66. Boscia F, Annunziato L, Taglialatela M. Retigabine and flupirtine exert neuroprotective actions in organotypic hippocampal cultures. Neuropharmacology. 2006 Aug;51(2):283–94. Rivas-Ramirez P, Reboreda A, Rueda-Ruzafa L, Herrera-Perez S, Lamas JA. Contribution of KCNQ and TREK channels to the resting membrane potential in sympathetic neurons at physiological temperature. Int J Mol Sci. 2020 Aug 12;21(16):5796. Seo MS, An JR, Jung HS, Jung WK, Choi IW, Na SH, et al. The muscarinic receptor antagonist tolterodine inhibits voltage-dependent K(+) channels in rabbit coronary arterial smooth muscle cells. Eur J Pharmacol. 2020 Mar 5;870:172921. Martin-Batista E, Manville RW, Rivero-Perez B, Bartolome-Martin D, Alvarez de la Rosa D, Abbott GW, et al. Activation of SGK1.1 upregulates the M-current in the presence of epilepsy mutations. Front Mol Neurosci. 2021;14:798261. Carver CM, Shapiro MS. Gq-coupled muscarinic receptor enhancement of KCNQ2/3 channels and activation of TRPC channels in multimodal control of excitability in dentate gyrus granule cells. J Neurosci. 2019 Feb 27;39(9):1566–87. Gomis-Perez C, Urrutia J, Marce-Grau A, Malo C, Lopez-Laso E, Felipe-Rucian A, et al. Homomeric Kv7.2 current suppression is a common feature in KCNQ2 epileptic encephalopathy. Epilepsia. 2019 Jan;60(1):139–48. Kojima T, Wasano K, Takahashi S, Homma K. Cell death-inducing cytotoxicity in truncated KCNQ4 variants associated with DFNA2 hearing loss. Dis Model Mech. 2021 Nov 1;14(11):dmm049015. Li J, Maghera J, Lamothe SM, Marco EJ, Kurata HT. Heteromeric assembly of truncated neuronal Kv7 channels: implications for neurologic disease and pharmacotherapy. Mol Pharmacol. 2020 Sep;98(3):192–202. Gamal El-Din TM, Lantin T, Tschumi CW, Juarez B, Quinlan M, Hayano JH, et al. Autism-associated mutations in Kv7 channels induce gating pore current. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45):e2112666118. Article / Publication Details

First-Page Preview

Received: March 25, 2022
Accepted: October 05, 2022
Published online: December 14, 2022

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.