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Remodeling of ion channel expression may contribute to electrophysiological consequences caused by methamphetamine in vitro and in vivo.

Abstract：

:Methamphetamine (MA) is a psychostimulant. MA may induce numerous cardiotoxic effects, leading to cardiac arrhythmias, heart failure, eventually leading to sudden cardiac death. The deleterious effects of methamphetamine work in tandem to disrupt the coordinated electrical activity of the heart and have been associated with life-threatening cardiac arrhythmias. Remodeling of ion channels is an important mechanism of arrhythmia. Although arrhythmogenic remodeling involves alterations in ion channel expression, it is yet unknown whether MA induced electrical remodeling by affecting gene expression, and whether the changes in protein expression are paralleled by alterations in mRNA expression. Our study focused on the expression of ion channels which were correlated to the electrical remodeling caused by MA. We used RT-PCR and western blot to assess of the transcript and translate levels of ion channel subunits, including Ito: kv1.4, kv1.7, kv3.4, kv4.2; IK1: kir2.1, kir2.2, kir2.3, kir2.4; and ICa-l: Ca(2+)α1, Ca(2+)β, respectively. The reversible effect of these changes after MA withdrawal was also evaluated. MA caused decrease in mRNA and protein levels in all ion channel subunits in vitro and also in vivo, is at this work. The kv3.4 and all 4 subunits of Kir2.0 family showed significant decrease than the other genes. Most of the channel subunit expression started to reverse after MA withdrawal for 4 weeks and significantly reverse in all of the channel subunits after MA withdrawal for 8 weeks. We found that CACNA1C and Kir2.0 family showed lower recoverability than the others after MA withdrawal for 8 weeks. The reduction of the ion channel expression levels may be the molecular mechanism that mediates the electrical remodeling caused by methamphetamine.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Qu YH,Leung KP,Qiao DF,Li DR,Liu C,Yue X,Wang HJ

doi

10.1016/j.bbrc.2013.11.114

subject

Has Abstract

pub_date

2014-01-10 00:00:00

pages

441-6

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)02026-3

journal_volume

443

pub_type

杂志文章

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Remodeling of ion channel expression may contribute to electrophysiological consequences caused by methamphetamine in vitro and in vivo.