Protein kinase C-epsilon primes the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to modulation by isoflurane. Anesthesiology 2004 Aug;101(2):381-9
Date
07/28/2004Pubmed ID
15277921DOI
10.1097/00000542-200408000-00019Scopus ID
2-s2.0-3343026158 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
BACKGROUND: Cardioprotection by volatile anesthetic-induced preconditioning is known to involve intracellular signaling pathways. Recent studies have shown that protein kinase C (PKC) plays an important role in anesthetic-induced preconditioning. In this study, the effects of the activation of specific isozymes of PKC, specifically PKC-epsilon and -delta, on the modulation of the sarcolemmal adenosine triphosphate-sensitive potassium (sarcKATP) channel by isoflurane were investigated.
METHODS: The sarcKATP current was measured in ventricular myocytes isolated from guinea pig hearts using the whole cell configuration of the patch clamp technique. Peptides that induced the translocation of specific PKC isozymes were used to activate PKC-epsilon and PKC-delta.
RESULTS: Under whole cell conditions, isoflurane alone was unable to elicit the opening of the sarcKATP channel. Pretreatment with the specific PKC-epsilon activator, PP106, primed the sarcKATP channel to open in the presence of isoflurane. The resulting sarcKATP current densities in the presence of 0.88 mm isoflurane were 6.5 +/- 6.0 pA/pF (n = 7) and 40.4 +/- 18.2 pA/pF (n = 7) after pretreatment with 100 and 200 nm PP106, respectively. The PKC-epsilon antagonist PP93 abolished this effect. A scrambled peptide of the PKC-epsilon activator PP105 did not prime the sarcKATP channel. The PKC-delta activator PP114 was significantly less effective in priming the sarcKATP channel. 5-Hydroxydecanoate significantly attenuated the effect of the PKC-epdsilon activator on the sarcKATP channel. In addition, immunohistochemical analysis showed that the PKC-epsilon isoform translocated to both the mitochondria and sarcolemma after anesthetic-induced preconditioning, whereas the PKC-delta isoform translocated to the mitochondria.
CONCLUSION: The PKC-epsilon isozyme primed the sarcKATP channel to open in the presence of isoflurane. The PKC-delta isozyme was significantly less effective in modulating the isoflurane effect on this channel.
Author List
Aizawa K, Turner LA, Weihrauch D, Bosnjak ZJ, Kwok WMAuthors
Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of WisconsinWai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
ATP-Binding Cassette TransportersAnesthetics, Inhalation
Animals
Cell Separation
Decanoic Acids
Electrophysiology
Enzyme Inhibitors
Female
Fluorescent Antibody Technique
Guinea Pigs
Heart
Hydroxy Acids
Immunohistochemistry
In Vitro Techniques
Isoflurane
KATP Channels
Male
Myocardium
Patch-Clamp Techniques
Phorbol Esters
Potassium Channels
Potassium Channels, Inwardly Rectifying
Protein Kinase C
Protein Kinase C-delta
Protein Kinase C-epsilon
Protein Transport
Sarcoplasmic Reticulum
