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Cardioprotection via activation of protein kinase C-delta depends on modulation of the reverse mode of the Na+/Ca2+ exchanger.
- Source :
-
Circulation [Circulation] 2006 Jul 04; Vol. 114 (1 Suppl), pp. I226-32. - Publication Year :
- 2006
-
Abstract
- Background: Pretreatment with the volatile anesthetic sevoflurane protects cardiomyocytes against subsequent ischemic episodes caused by a protein kinase C (PKC)-delta mediated preconditioning effect. Sevoflurane directly modulates cardiac Ca2+ handling, and because Ca2+ also serves as a mediator in other cardioprotective signaling pathways, possible involvement of the Na+/Ca2+ exchanger (NCX) in relation with PKC-delta in sevoflurane-induced cardioprotection was investigated.<br />Methods and Results: Isolated right ventricular rat trabeculae were subjected to simulated ischemia and reperfusion (SI/R), consisting of superfusion with hypoxic glucose-free buffer for 40 minutes after rigor development, followed by reperfusion with normoxic glucose containing buffer. Preconditioning with sevoflurane before SI/R improved isometric force development during contractile recovery at 60 minutes after the end of hypoxic superfusion (83+/-7% [sevo] versus 57+/-2% [SI/R];n=8; P<0.01). Inhibition of the reverse mode of the NCX by KB-R7943 (10 micromol/L) or SEA0400 (1 micromol/L) during preconditioning attenuated the protective effect of sevoflurane. KB-R7943 and SEA0400 did not have intrinsic effects on the contractile recovery. Furthermore, inhibition of the NCX in trabeculae exposed to sevoflurane reduced sevoflurane-induced PKC-delta translocation toward the sarcolemma, as demonstrated by digital imaging fluorescent microscopy. The degree of PKC-delta phosphorylation at serine643 as determined by western blot analysis was not affected by sevoflurane.<br />Conclusions: Sevoflurane-induced cardioprotection depends on the NCX preceding PKC-delta translocation presumably via increased NCX-mediated Ca2+ influx. This may suggest that increased myocardial Ca2+ load triggers the cardioprotective signaling cascade elicited by volatile anesthetic agents similar to other modes of preconditioning.
- Subjects :
- Anesthetics, Inhalation pharmacology
Aniline Compounds pharmacology
Animals
Calcium Signaling drug effects
Cardiotonic Agents pharmacology
Enzyme Activation
Glucose pharmacology
Heart Ventricles drug effects
Heart Ventricles enzymology
In Vitro Techniques
Male
Methyl Ethers pharmacology
Myocardial Reperfusion Injury enzymology
Phenyl Ethers pharmacology
Phosphorylation drug effects
Phosphoserine analysis
Protein Processing, Post-Translational drug effects
Protein Transport drug effects
Rats
Rats, Wistar
Sarcolemma enzymology
Sevoflurane
Signal Transduction drug effects
Signal Transduction physiology
Sodium-Calcium Exchanger antagonists & inhibitors
Thiourea analogs & derivatives
Thiourea pharmacology
Anesthetics, Inhalation therapeutic use
Calcium Signaling physiology
Cardiotonic Agents therapeutic use
Ischemic Preconditioning, Myocardial methods
Methyl Ethers therapeutic use
Myocardial Ischemia enzymology
Myocardial Reperfusion Injury prevention & control
Protein Kinase C-delta physiology
Sodium-Calcium Exchanger physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 114
- Issue :
- 1 Suppl
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 16820577
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.105.000570