Faculty Collaboration Database

The interaction of isoflurane and protein kinase C-activators on sarcolemmal KATP channels. Anesth Analg 2005 Jun;100(6):1680-1686

Date

05/28/2005

Pubmed ID

15920195

DOI

10.1213/01.ANE.0000152187.17759.F6

Scopus ID

2-s2.0-19044394666 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Protein kinase C (PKC)-dependent signaling pathways may be involved in the "memory" effect of anesthetic and ischemic preconditioning, which facilitates activation of cardioprotective adenosine triphosphate (ATP)-sensitive potassium channels during later ischemic challenge and ATP depletion. Using patch-clamp techniques, we found that exposure of isolated guinea pig cardiomyocytes to 1 mM of isoflurane after phorbol ester stimulation of PKC facilitates the induction of larger (P < or = 0.05) sarcolemmal K(ATP) channel currents (IKATP) during cell dialysis with 0.5, compared to 1.0, mM of ATP in the pipette (10 +/- 5 versus 2 +/- 1 pA/pF in five and six cells, respectively). A PKC inhibitor, bisindolylmaleimide, abolished the induction of IKATP by a second brief isoflurane exposure under these conditions. A diacylglycerol PKC activator applied via the pipette elicited concentration-related activation of IKATP. The diacylglycerol alone (0.5 microM) elicited I(KATP), averaging 5 +/- 3 pA/pF in nine cells. Briefly treating myocytes on the microscope stage with isoflurane, followed by washout and patching with the same diacylglycerol solution, elicited larger (P < or = 0.01) IKATP, averaging 40 +/- 9 pA/pF (10 cells), with an onset 48 +/- 2 min after anesthetic pretreatment. Facilitation of IKATP by isoflurane during the reduction of intracellular ATP is dependent on PKC, whereas "preconditioning" myocytes with isoflurane causes persistent changes in sarcolemmal KATP channel function, which enhance the induction of IKATP by a diacylglycerol.

Author List

Turner LA, Fujimoto K, Suzuki A, Stadnicka A, Bosnjak ZJ, Kwok WM

Authors

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Alkaloids
Anesthetics, Inhalation
Animals
Benzophenanthridines
Dialysis
Diglycerides
Electrophysiology
Enzyme Activation
Enzyme Inhibitors
Guinea Pigs
In Vitro Techniques
Indoles
Isoflurane
Male
Maleimides
Membrane Potentials
Membrane Proteins
Phenanthridines
Potassium Channels
Protein Kinase C
Sarcolemma
Tetradecanoylphorbol Acetate