Growth hormone secretagogues preserve the electrophysiological properties of mouse cardiomyocytes isolated from in Vitro ischemia/reperfusion heart

Ma, Yi, Zhang, Lin, Launikonis, Bradley S. and Chen, Chen (2012) Growth hormone secretagogues preserve the electrophysiological properties of mouse cardiomyocytes isolated from in Vitro ischemia/reperfusion heart. Endocrinology, 153 11: 5480-5490. doi:10.1210/en.2012-1404


Author Ma, Yi
Zhang, Lin
Launikonis, Bradley S.
Chen, Chen
Title Growth hormone secretagogues preserve the electrophysiological properties of mouse cardiomyocytes isolated from in Vitro ischemia/reperfusion heart
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2012-11-01
Sub-type Article (original research)
DOI 10.1210/en.2012-1404
Volume 153
Issue 11
Start page 5480
End page 5490
Total pages 11
Place of publication Chevy Chase, MD United States
Publisher The Endocrine Society
Language eng
Formatted abstract
Ischemic heart diseases often induce cardiac arrhythmia with irregular cardiac action potential (AP). This study aims to demonstrate that GH secretagogues (GHS) ghrelin and its synthetic analog hexarelin can preserve the electrophysiological properties of cardiomyocytes experiencing ischemia/ reperfusion (I/R). Isolated hearts from adult male mice underwent 20 min global ischemia followed by 30 min reperfusion using a Langendorff apparatus. Ghrelin (10 nM) or hexarelin (1 nM) was administered in the perfusion solution either 10 min before or after ischemia, termed pre- or posttreatments. Cardiomyocytes isolated from these hearts were used for whole-cell patch clamping to measure AP, voltage-gated L-type calcium current (ICaL), transient outward potassium current (Ito), and sodium current (INa). AP amplitude and duration were significantly decreased by I/R, butGHStreatments maintained their normality.GHStreatments prevented the decrease in ICaL and INa after I/R, thereby maintaining AP amplitude. Although the significant increase in Ito after I/R partially explained the shortened AP duration, the normalization of it by GHS treatments might contribute to the preservation of AP duration. Phosphorylated p38 and c-Jun NH2-terminal kinase andthedownstreamactive caspase-9 in the cellular apoptosispathwayweresignificantly increased after I/R but not when GHS treatments were included, whereas phosphorylation of ERK1/2 associated with cell survival showed increase after I/R and a further increase after GHS treatments by binding to its receptor GHS receptor type 1a. These results suggest GHS can not only preserve the electrophysiological properties of cardiomyocytes after I/R but also inhibit cardiomyocyte apoptosis and promote cell survival by modification of MAPK pathways through activating GHS receptor type 1a.
Keyword Rat ventricular myocytes
Myocardial reperfusion injury
Ischemia reperfusion
Cardiac ischemia
Cell-death
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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