title: 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.
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China.
authors: Yi-Hong
authors: YH
authors: Qu
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China.
authors: Ka-Pui
authors: KP
authors: Leung
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China.
authors: Dong-Fang
authors: DF
authors: Qiao
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China; Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, 545-8585 Osaka, Japan.
authors: Dong-Ri
authors: DR
authors: Li
authors: Guangzhou Forensic Science Institute, Guangzhou 510030, Guangdong Province, PR China.
authors: Chao
authors: C
authors: Liu
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China. Electronic address: yiluyangguang@163.com.
authors: Xia
authors: X
authors: Yue
authors: Department of Forensic Medicine, Southern Medical University, No.1838, Guangzhou 510515, Guangdong Province, PR China. Electronic address: hjwang711@163.com.
authors: Hui-Jun
authors: HJ
authors: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D015221:Potassium Channels; D008694:Methamphetamine
keywords: Arrhythmias; Calcium channel; Cardiotoxicity; I(Ca-)(l); I(K1); I(to); L-type calcium current; MA; Methamphetamine; NRVMs; Potassium channel; QTc; corrected QT interval; inwardly rectifying potassium current; methamphetamine; neonatal rat ventricular myocytes; transient outward potassium current