K(ATP) channel gene expression is induced by urocortin and mediates its cardioprotective effect.
BACKGROUND
Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.


RESULTS
We have analyzed global changes in gene expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K(ATP) channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.


CONCLUSIONS
This is, to our knowledge, the first report of the altered expression of a K(ATP) channel subunit induced by a cardioprotective agent and demonstrates that K(ATP) channel opening is essential for the effect of this novel cardioprotective agent.
Lawrence
K M
KM
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, England.
Chanalaris
A
A
Scarabelli
T
T
Hubank
M
M
Pasini
E
E
Townsend
P A
PA
Comini
L
L
Ferrari
R
R
Tinker
A
A
Stephanou
A
A
Knight
R A
RA
Latchman
D S
DS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D020869:Gene Expression Profiling; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation; D054832:Urocortins
D002316:Cardiotonic Agents; D016207:Cytokines; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D054832:Urocortins; D000255:Adenosine Triphosphate; D003346:Corticotropin-Releasing Hormone; C092073:cardiotrophin 1