N-benzhydryl quinuclidine compounds are a potent and Src kinase-independent inhibitor of NALCN channels.
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
01
10
2019
revised:
01
05
2020
accepted:
06
05
2020
pubmed:
22
5
2020
medline:
22
6
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
NALCN is a Na The effect of N-benzhydryl quinuclidine compounds on NALCN channels was demonstrated using whole-cell patch-clamp recordings in HEK293T cells overexpressing NALCN and acutely isolated nigral dopaminergic neurons that express NALCN endogenously. Src kinase activity was measured using a Src kinase assay kit, and voltage and current-clamp recordings from nigral dopaminergic neurons were used to measure NALCN currents and membrane potentials. N-benzhydryl quinuclidine compounds inhibited NALCN channels without affecting TRPC channels, another important route for Na These findings suggest that N-benzhydryl quinuclidine compounds have a pharmacological potential to directly inhibit NALCN channels and could be a useful tool to investigate functions of NALCN channels.
Sections du résumé
BACKGROUND AND PURPOSE
NALCN is a Na
EXPERIMENTAL APPROACH
The effect of N-benzhydryl quinuclidine compounds on NALCN channels was demonstrated using whole-cell patch-clamp recordings in HEK293T cells overexpressing NALCN and acutely isolated nigral dopaminergic neurons that express NALCN endogenously. Src kinase activity was measured using a Src kinase assay kit, and voltage and current-clamp recordings from nigral dopaminergic neurons were used to measure NALCN currents and membrane potentials.
KEY RESULTS
N-benzhydryl quinuclidine compounds inhibited NALCN channels without affecting TRPC channels, another important route for Na
CONCLUSION AND IMPLICATIONS
These findings suggest that N-benzhydryl quinuclidine compounds have a pharmacological potential to directly inhibit NALCN channels and could be a useful tool to investigate functions of NALCN channels.
Identifiants
pubmed: 32436268
doi: 10.1111/bph.15104
pmc: PMC7402281
doi:
Substances chimiques
Benzhydryl Compounds
0
Ion Channels
0
Membrane Proteins
0
NALCN protein, human
0
Quinuclidines
0
src-Family Kinases
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3795-3810Subventions
Organisme : National Research Foundation of Korea
ID : 2017R1A2B3005656
Informations de copyright
© 2020 The British Pharmacological Society.
Références
Elife. 2016 May 13;5:
pubmed: 27177420
J Neurosci. 2003 Mar 1;23(5):1557-62
pubmed: 12629156
Br J Pharmacol. 2019 Dec;176 Suppl 1:S297-S396
pubmed: 31710714
Nucleic Acids Res. 2018 Jan 4;46(D1):D1091-D1106
pubmed: 29149325
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1092-7
pubmed: 26755577
Physiol Genomics. 2011 Mar 16;43(5):265-70
pubmed: 21177381
Pharmacol Ther. 1998 Aug;79(2):89-104
pubmed: 9749878
Annu Rev Physiol. 2003;65:453-80
pubmed: 12471170
J Invest Dermatol. 2006 Sep;126(9):1982-93
pubmed: 16741513
Mol Pharmacol. 1992 Sep;42(3):458-63
pubmed: 1383685
J Neurosci. 2010 May 26;30(21):7401-13
pubmed: 20505107
Front Cell Neurosci. 2014 May 20;8:132
pubmed: 24904279
J Neurosci. 2000 Dec 15;20(24):9004-16
pubmed: 11124976
Channels (Austin). 2009 May-Jun;3(3):161-3
pubmed: 19535918
J Neurophysiol. 1995 Sep;74(3):1137-48
pubmed: 7500139
Cell Physiol Biochem. 2012;29(3-4):501-10
pubmed: 22508057
Sci Rep. 2015 Oct 05;5:14773
pubmed: 26435058
Br J Pharmacol. 2019 Dec;176 Suppl 1:S142-S228
pubmed: 31710715
EMBO Rep. 2009 Aug;10(8):873-80
pubmed: 19575010
Am J Physiol Gastrointest Liver Physiol. 2003 Apr;284(4):G604-16
pubmed: 12631560
Nat Commun. 2017 Dec 12;8(1):2077
pubmed: 29233994
Br J Pharmacol. 2018 Apr;175(7):987-993
pubmed: 29520785
J Cell Sci. 2003 Jul 1;116(Pt 13):2665-75
pubmed: 12746490
Br J Pharmacol. 2020 Aug;177(16):3795-3810
pubmed: 32436268
FEBS Lett. 1999 Feb 26;445(2-3):231-6
pubmed: 10094463
Neuron. 2007 May 24;54(4):505-7
pubmed: 17521564
Neuron. 2011 Dec 22;72(6):899-911
pubmed: 22196327
Cell. 2007 Apr 20;129(2):371-83
pubmed: 17448995
Nature. 2009 Feb 5;457(7230):741-4
pubmed: 19092807
Neuron. 2000 Apr;26(1):35-43
pubmed: 10798390
Cell. 2015 Aug 13;162(4):836-48
pubmed: 26276633
J Physiol. 2014 Jul 1;592(13):2829-44
pubmed: 24756642
PLoS One. 2013 Nov 05;8(11):e78147
pubmed: 24223770
Curr Biol. 2007 Sep 18;17(18):1595-600
pubmed: 17825559
Gastroenterology. 2009 Oct;137(4):1415-24
pubmed: 19549525
Mol Pharmacol. 2014 Dec;86(6):760-72
pubmed: 25267719
Br J Pharmacol. 2010 Aug;160(7):1577-9
pubmed: 20649561
PLoS Biol. 2008 Mar 11;6(3):e55
pubmed: 18336069
Eur J Neurosci. 2007 Nov;26(10):2950-61
pubmed: 18001290
J Neurosci. 2004 Sep 15;24(37):7985-98
pubmed: 15371499
Mol Pharmacol. 2003 Dec;64(6):1271-6
pubmed: 14645655
Sci Rep. 2019 Aug 13;9(1):11791
pubmed: 31409833
J Biol Chem. 2012 May 18;287(21):17029-39
pubmed: 22457348
Nature. 2001 Jun 21;411(6840):962-5
pubmed: 11418862
Br J Pharmacol. 2018 Feb;175(3):407-411
pubmed: 29350411
Neuron. 2017 Apr 19;94(2):294-303.e4
pubmed: 28392070
Annu Rev Physiol. 1996;58:349-62
pubmed: 8815799
Curr Biol. 2007 Apr 3;17(7):624-9
pubmed: 17350263
Neuron. 1989 Aug;3(2):153-61
pubmed: 2560389
Br J Pharmacol. 2019 Dec;176 Suppl 1:S21-S141
pubmed: 31710717
J Med Genet. 2013 Aug;50(8):515-20
pubmed: 23749988
J Neurosci. 2005 Sep 7;25(36):8272-81
pubmed: 16148235
J Pharmacol Toxicol Methods. 2005 May-Jun;51(3):187-200
pubmed: 15862464
Annu Rev Physiol. 2013;75:155-79
pubmed: 22974438
J Physiol. 2007 Jun 1;581(Pt 2):709-24
pubmed: 17379636
J Neurosci. 2016 Aug 3;36(31):8174-87
pubmed: 27488637
Neuron. 2010 Nov 4;68(3):488-99
pubmed: 21040849
J Pharmacol Exp Ther. 1993 Jan;264(1):1-5
pubmed: 8380855