Premium
Isoflurane Preconditioning Delays Opening of Mitochondrial Permeability Transition Pore via Protein Kinase C Signaling Pathway
Author(s) -
Pravdic Danijel,
Sedlic Filip,
Mueller Samantha J,
Bosnjak Zeljko J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.750.13
Subject(s) - mptp , isoflurane , mitochondrial permeability transition pore , chemistry , depolarization , protein kinase c , chelerythrine , anesthetic , biophysics , pharmacology , kinase , biochemistry , apoptosis , biology , anesthesia , programmed cell death , endocrinology , medicine , dopamine , dopaminergic , organic chemistry
Isoflurane protects the myocardium from ischemia and reperfusion (I/R) injury via protein kinase C (PKC) signaling pathway. It has been suggested that the mitochondrial permeability transition pore (mPTP) is the end effector of I/R injury, whereas PKC has a protective effect by blocking mPTP opening. Here we investigated whether anesthetic preconditioning (APC) with isoflurane delays mPTP opening and whether the PKC plays a role in isoflurane‐induced delay in mPTP opening. Isoflurane preconditioned rat cardiomyocytes were loaded with fluorescent probe tetramethylrhodamine ethyl ester (TMRE) and subjected to a simulated I/R injury by laser‐induced ROS production. Using the laser‐scanning confocal microscopy, we measured the time to 50% decrease in TMRE fluorescence, which coincides with depolarization of the mitochondria and represents an opening of mPTP. To confirm the role of mPTP, we used cyclosporine A (CsA). The role of PKC was tested using the non‐specific PKC inhibitor chelerythrine (CHEL). APC with isoflurane prolonged the mean depolarization time of the control fluorescence of 216±8 s, to 261±16 s. A similar time delay of 279±22 s was found in cells pretreated with CsA. Isoflurane‐induced delay in an mPTP opening was abrogated to 219±7 s in cells treated with CHEL. In conclusion, our results indicate that APC with isoflurane delays the opening of mPTP in a PKC‐dependent manner. Supported by NIH (HL 034708 and GM 066730)