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Query: UMLS:C0151744 (
myocardial ischemia
)
31,282
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The cardiac ATP-sensitive potassium (KATP) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (
SUR2
). This channel is activated during
myocardial ischemia
and protects the heart from ischemic injury. We examined the transcriptional expression of these genes in rats with
myocardial ischemia
. 60 min of myocardial regional ischemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (approximately 2.7-3.1-fold) but also in the nonischemic (approximately 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion also induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 min of ischemia followed by 24 h of reperfusion did not induce such expression. In contrast, mRNAs for Kir6.2 and
SUR2
remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged
myocardial ischemia
rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression.
...
PMID:Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts. 939 52
ATP-sensitive K(+) (K(ATP)) channels, composed of inward rectifier K(+) (Kir)6.x and sulfonylurea receptor (SUR)x subunits, are expressed on cellular plasma membranes. We demonstrate an essential role for
SUR2
subunits in trafficking K(ATP) channels to an intracellular vesicular compartment. Transfection of Kir6.x/
SUR2
subunits into a variety of cell lines (including h9c2 cardiac cells and human coronary artery smooth muscle cells) resulted in trafficking to endosomal/lysosomal compartments, as assessed by immunofluorescence microscopy. By contrast, SUR1/Kir6.x channels efficiently localized to the plasmalemma. The channel turnover rate was similar with SUR1 or
SUR2
, suggesting that the expression of Kir6/
SUR2
proteins in lysosomes is not associated with increased degradation. Surface labeling of hemagglutinin-tagged channels demonstrated that
SUR2
-containing channels dynamically cycle between endosomal and plasmalemmal compartments. In addition, Kir6.2 and
SUR2
subunits were found in both endosomal and sarcolemmal membrane fractions isolated from rat hearts. The balance of these K(ATP) channel subunits shifted to the sarcolemmal membrane fraction after the induction of ischemia. The K(ATP) channel current density was also increased in rat ventricular myocytes isolated from hearts rendered ischemic before cell isolation without corresponding changes in subunit mRNA expression. We conclude that an intracellular pool of
SUR2
-containing K(ATP) channels exists that is derived by endocytosis from the plasma membrane. In cardiac myocytes, this pool can potentially play a cardioprotective role by serving as a reservoir for modulating surface K(ATP) channel density under stress conditions, such as
myocardial ischemia
.
...
PMID:Endosomal KATP channels as a reservoir after myocardial ischemia: a role for SUR2 subunits. 2105 44
ATP-sensitive potassium channels found in both the sarcolemma (sarcK
ATP
) and mitochondria (mitoK
ATP
) of cardiomyocytes are important mediators of cardioprotection during
ischemic heart disease
. Sulfonylurea receptor isoforms (
SUR2
), encoded by
Abcc9
, an ATP-binding cassette family member, form regulatory subunits of the sarcK
ATP
channel and are also thought to regulate mitoK
ATP
channel activity. A short-form splice variant of
SUR2
(SUR2A-55) was previously shown to target mitochondria and display diaxoxide and ATP insensitive K
ATP
activity when co-expressed with the inward rectifier channels Kir6.2 and Kir6.1. We hypothesized that mice with cardiac specific overexpression of SUR2A-55 would mediate cardioprotection from ischemia by altering mitoK
ATP
properties. Mice overexpressing SUR2A-55 (TG
SUR2A-55
) in cardiomyocytes were generated and showed no significant difference in echocardiographic measured chamber dimension, percent fractional shortening, heart to body weight ratio, or gross histologic features compared to normal mice at 11-14 weeks of age. TG
SUR2A-55
had improved hemodynamic functional recovery and smaller infarct size after ischemia reperfusion injury compared to WT mice in an isolated hanging heart model. The mitochondrial membrane potential of TG
SUR2A-55
mice was less sensitive to ATP, diazoxide, and Ca
2+
loading. These data suggest that the SUR2A-55 splice variant favorably affects mitochondrial function leading to cardioprotection. These data support a role for the regulation of mitoK
ATP
activity by SUR2A-55.
...
PMID:Transgenic overexpression of the SUR2A-55 splice variant in mouse heart reduces infract size and promotes protective mitochondrial function. 2999 96
