دورية أكاديمية
أعرض في EDS

Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome.

التفاصيل البيبلوغرافية
العنوان: Delayed Ventricular Repolarization and Sodium Channel Current Modification in a Mouse Model of Rett Syndrome.
المؤلفون: Cheng H; School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK., Charles I; School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK., James AF; School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK., Abdala AP; School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK., Hancox JC; School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol BS8 1TD, UK.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2022 May 20; Vol. 23 (10). Date of Electronic Publication: 2022 May 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Long QT Syndrome* , Rett Syndrome*/genetics, Animals ; Disease Models, Animal ; Male ; Mice ; Ranolazine ; Sodium ; Sodium Channels
مستخلص: Rett syndrome (RTT) is a severe developmental disorder that is strongly linked to mutations in the MECP2 gene. RTT has been associated with sudden unexplained death and ECG QT interval prolongation. There are mixed reports regarding QT prolongation in mouse models of RTT, with some evidence that loss of Mecp2 function enhances cardiac late Na current, I Na,Late . The present study was undertaken in order to investigate both ECG and ventricular AP characteristics in the Mecp2 Null/Y male murine RTT model and to interrogate both fast I Na and I Na,Late in myocytes from the model. ECG recordings from 8-10-week-old Mecp2 Null/Y male mice revealed prolongation of the QT and rate corrected QT (QTc) intervals and QRS widening compared to wild-type (WT) controls. Action potentials (APs) from Mecp2 Null/Y myocytes exhibited longer APD 75 and APD 90 values, increased triangulation and instability. I Na,Late was also significantly larger in Mecp2 Null/Y than WT myocytes and was insensitive to the Nav1.8 inhibitor A-803467. Selective recordings of fast I Na revealed a decrease in peak current amplitude without significant voltage shifts in activation or inactivation V 0.5 . Fast I Na 'window current' was reduced in RTT myocytes; small but significant alterations of inactivation and reactivation time-courses were detected. Effects of two I Na,Late inhibitors, ranolazine and GS-6615 (eleclazine), were investigated. Treatment with 30 µM ranolazine produced similar levels of inhibition of I Na,Late in WT and Mecp2 Null/Y myocytes, but produced ventricular AP prolongation not abbreviation. In contrast, 10 µM GS-6615 both inhibited I Na,Late and shortened ventricular AP duration. The observed changes in I Na and I Na,Late can account for the corresponding ECG changes in this RTT model. GS-6615 merits further investigation as a potential treatment for QT prolongation in RTT.
References: Circ Res. 2001 Nov 23;89(11):944-56. (PMID: 11717150)
Expert Opin Investig Drugs. 2010 Dec;19(12):1465-74. (PMID: 21105855)
Folia Hered Pathol (Milano). 1969 Jul;18(3):115-23. (PMID: 5403918)
Cardiovasc Drugs Ther. 2013 Feb;27(1):61-8. (PMID: 23274937)
Dev Med Child Neurol. 2020 Jul;62(7):775. (PMID: 31985047)
Sci Rep. 2015 Jun 15;5:11204. (PMID: 26073556)
Pediatr Neurol. 2017 May;70:61-66. (PMID: 28351539)
Am J Med Genet A. 2017 Jun;173(6):1495-1501. (PMID: 28394409)
Neuromolecular Med. 2014 Jun;16(2):231-64. (PMID: 24615633)
Acta Physiol (Oxf). 2013 Dec;209(4):262-71. (PMID: 24119104)
Heart Rhythm. 2016 Mar;13(3):762-70. (PMID: 26598320)
Heart Rhythm. 2018 Feb;15(2):277-286. (PMID: 29017927)
Front Physiol. 2012 Jun 22;3:210. (PMID: 22737129)
J Cardiovasc Electrophysiol. 2007 Jun;18(6):655-7. (PMID: 17488264)
J Pediatr. 1994 Jul;125(1):80-2. (PMID: 8021793)
Heart Rhythm. 2009 Nov;6(11):1625-31. (PMID: 19879541)
Ann Neurol. 2010 Dec;68(6):944-50. (PMID: 21154482)
Heart Rhythm. 2017 Nov;14(11):1657-1664. (PMID: 28610990)
Am J Physiol Heart Circ Physiol. 2009 Sep;297(3):H1048-57. (PMID: 19592609)
J Mol Cell Cardiol. 2014 Sep;74:220-30. (PMID: 24877995)
Neurology. 2008 Apr 15;70(16):1313-21. (PMID: 18337588)
Am J Physiol. 1998 Mar;274(3):H747-51. (PMID: 9530184)
Heart. 2006 Jul;92 Suppl 4:iv1-iv5. (PMID: 16775091)
J Cardiovasc Pharmacol Ther. 2004 Sep;9 Suppl 1:S65-83. (PMID: 15378132)
Wien Med Wochenschr. 2016 Sep;166(11-12):322-4. (PMID: 27577062)
Heart Rhythm O2. 2020 Aug;1(3):206-214. (PMID: 32864638)
Br J Pharmacol. 2006 May;148(1):16-24. (PMID: 16520744)
Future Neurol. 2013 Jan 1;8(1):. (PMID: 24348096)
Nat Genet. 2001 Mar;27(3):322-6. (PMID: 11242117)
Br J Pharmacol. 2000 Aug;130(8):1753-66. (PMID: 10952663)
J Pharmacol Exp Ther. 2001 Sep;298(3):1067-82. (PMID: 11504804)
J Cardiovasc Electrophysiol. 2021 Nov;32(11):3057-3067. (PMID: 34427958)
Dis Model Mech. 2015 Apr;8(4):363-71. (PMID: 25713300)
Nat Genet. 1999 Oct;23(2):185-8. (PMID: 10508514)
Heart Rhythm. 2008 Jul;5(7):1019-26. (PMID: 18598958)
Eur J Paediatr Neurol. 2003;7(1):5-12. (PMID: 12615169)
Hum Mol Genet. 2000 May 22;9(9):1369-75. (PMID: 10814718)
Circ Res. 2012 Jul 20;111(3):322-32. (PMID: 22723299)
Circ Res. 1989 Feb;64(2):389-97. (PMID: 2536304)
Arch Dis Child. 1999 May;80(5):470-2. (PMID: 10208957)
Hum Mol Genet. 2000 May 22;9(9):1377-84. (PMID: 10814719)
Physiol Rev. 2021 Jul 1;101(3):1083-1176. (PMID: 33118864)
Hum Mutat. 2000 Apr;15(4):382-3. (PMID: 10737989)
Indian Pacing Electrophysiol J. 2009 Sep 01;9(5):260-7. (PMID: 19763194)
J Child Neurol. 2001 May;16(5):370-3. (PMID: 11392524)
Sci Transl Med. 2011 Dec 14;3(113):113ra125. (PMID: 22174313)
Cell. 2017 May 18;169(5):945-955.e10. (PMID: 28525759)
Pharmacol Ther. 2008 Sep;119(3):326-39. (PMID: 18662720)
Circulation. 2001 Apr 17;103(15):2004-13. (PMID: 11306531)
J Med Chem. 2016 Oct 13;59(19):9005-9017. (PMID: 27690427)
Science. 2007 Feb 23;315(5815):1143-7. (PMID: 17289941)
G Ital Cardiol (Rome). 2011 Oct;12(10 Suppl 2):3S-11S. (PMID: 21947134)
Pflugers Arch. 1996 Sep;432(5):930-7. (PMID: 8772145)
J Gen Physiol. 1985 Jul;86(1):89-104. (PMID: 2411848)
Ann N Y Acad Sci. 2012 Jul;1259:121-35. (PMID: 22758644)
Cardiovasc Res. 2006 Jan;69(1):116-27. (PMID: 16223473)
Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:71-4. (PMID: 9452925)
Dev Med Child Neurol. 2020 Jul;62(7):833-836. (PMID: 31797351)
Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1923-9. (PMID: 19767532)
Cardiovasc Res. 2012 Aug 1;95(3):300-7. (PMID: 22562703)
Am J Physiol Heart Circ Physiol. 2017 Jul 1;313(1):H190-H199. (PMID: 28476922)
Respir Physiol Neurobiol. 2013 Nov 1;189(2):280-7. (PMID: 23816600)
J Cardiovasc Pharmacol. 2008 Jun;51(6):581-9. (PMID: 18520952)
Sci Rep. 2017 Feb 02;7:41824. (PMID: 28150739)
Am J Respir Cell Mol Biol. 2014 Jun;50(6):1031-9. (PMID: 24351104)
معلومات مُعتمدة: PG/16/55/32277 United Kingdom BHF_ British Heart Foundation
فهرسة مساهمة: Keywords: GS-6615; INa; INa,Late; MECP2; QT interval; RTT; Rett syndrome; action potential; eleclazine; ranolazine; sodium channel
المشرفين على المادة: 0 (Sodium Channels)
9NEZ333N27 (Sodium)
A6IEZ5M406 (Ranolazine)
تواريخ الأحداث: Date Created: 20220528 Date Completed: 20220531 Latest Revision: 20220716
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9147596
DOI: 10.3390/ijms23105735
PMID: 35628543
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms23105735