RGD Reference Report - Ionic mechanisms underlying action potential prolongation by focal cerebral ischemia in rat ventricular myocytes. - Rat Genome Database

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Ionic mechanisms underlying action potential prolongation by focal cerebral ischemia in rat ventricular myocytes.

Authors: Wang, L  Sun, L  Zhang, Y  Wu, H  Li, C  Pan, Z  Lu, Y  Yang, B 
Citation: Wang L, etal., Cell Physiol Biochem. 2009;23(4-6):305-16. Epub 2009 May 6.
RGD ID: 6484225
Pubmed: PMID:19471098   (View Abstract at PubMed)
DOI: DOI:10.1159/000218177   (Journal Full-text)

Despite prolongation of the QTc interval in humans during cerebral ischemia, little is known about the mechanisms that underlie these actions. Cerebral ischemic model was established by middle cerebral artery occlusion (MCAO) for 24 h. In rat ventricular myocytes, the effect of cerebral ischemia on action potential duration (APD) and underlying electrophysiologic mechanisms were investigated by whole-cell patch clamp. We demonstrated that heart rate-corrected QT interval and APD were prolonged with frequent occurrence of ventricular tachyarrhythmias in a rat model of MCAO. The I(Na) density was overall smaller in cerebral ischemic myocytes relative to sham myocytes (P < 0.01). The Nav1.5 protein and mRNA levels (pore-forming subunit for I(Na) ) were decreased by about 20% (P < 0.01) in cerebral ischemic rat hearts than those in sham-operated rat hearts. Peak transient outward K(+) current (I(to)) at +60 mV was found decreased by approximately 32.3% (P < 0.01) in cerebral ischemic rats. The peak amplitude of L-type Ca(2+) current (I(Ca,L)) was increased and the inactivation kinetics were slowed (P < 0.01). Protein level of the pore-forming subunit for I(to) was decreased, but that for I(Ca,L) was increased. The inward rectifier K(+) current (I(K1)) at -120 mV and its protein level were unaffected. Our study represents the first documentation of I(Na), I(to) and I(Ca,L) channelopathy as the major ionic mechanism for cerebral ischemic QT prolongation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain ischemia  ISOScn5a (Rattus norvegicus)6484225; 6484225 RGD 
brain ischemia  IEP 6484225 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Scn5a  (sodium voltage-gated channel alpha subunit 5)

Genes (Mus musculus)
Scn5a  (sodium channel, voltage-gated, type V, alpha)

Genes (Homo sapiens)
SCN5A  (sodium voltage-gated channel alpha subunit 5)


Additional Information