Faculty Collaboration Database

Contribution of reactive oxygen species to isoflurane-induced sensitization of cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to pinacidil. Anesthesiology 2004 Mar;100(3):575-80

Date

04/28/2004

Pubmed ID

15108971

DOI

10.1097/00000542-200403000-00017

Scopus ID

2-s2.0-1442357298 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: Myocardial protection by volatile anesthetics involves activation of cardiac adenosine triphosphate-sensitive potassium (K(ATP)) channels. The authors have previously shown that isoflurane enhances sensitivity of the sarcolemmal K(ATP) channel to the opener, pinacidil. Because reactive oxygen species seem to be mediators in anesthetic preconditioning, the authors investigated whether they contribute to the mechanism of the sensitization effect by isoflurane.

METHODS: Ventricular myocytes were isolated from guinea pig hearts for the whole cell patch clamp recordings of the sarcolemmal K(ATP) channel current (I(KAPT)). Free radical scavengers N-acetyl-L-cysteine, carnosine, superoxide dismutase, and catalase were used to investigate whether reactive oxygen species mediate isoflurane facilitation of the channel opening by pinacidil. A possible role of the mitochondrial K(ATP) channels was tested using a blocker of these channels, 5-hydroxydecanoate.

RESULTS: The mean density (+/- SEM) of I(KAPT) elicited by pinacidil (20 microM) was 18.9 +/- 1.8 pA/pF (n = 11). In the presence of isoflurane (0.55 mM), the density of pinacidil-activated I(KAPT) increased to 38.5 +/- 2.4 pA/pF (n = 9). Concurrent application of isoflurane and N-acetyl-L-cysteine decreased the sensitization effect by isoflurane in a concentration-dependent manner, whereby the densities of I(KAPT) were 32.6 +/- 1.4 (n = 6), 26.2 +/- 2.3 (n = 6), and 19.4 +/- 2.1 pA/pF (n = 8) at 100, 250, and 500 microM N-acetyl-L-cysteine, respectively. Concurrent application of isoflurane and carnosine (100 microM), superoxide dismutase (100 U/ml), or catalase (100 U/ml) attenuated the densities of I(KAPT) to 27.9 +/- 2.6, 27.2 +/- 2.9, and 25.9 +/- 2.2 pA/pF, respectively. None of the scavengers affected activation of I(KAPT) by pinacidil alone. 5-Hydroxydecanoate (100 microM) did not alter the sensitization effect by isoflurane, and the density of I(KAPT) in this group was 37.1 +/- 3.8 pA/pF (n= 6).

CONCLUSION: These results suggest that reactive oxygen species contribute to the mechanism by which isoflurane sensitizes the cardiac sarcolemmal K(ATP) channel to the opener, pinacidil.

Author List

An J, Stadnicka A, Kwok WM, Bosnjak ZJ

Author

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

Acetylcysteine
Anesthetics, Inhalation
Animals
Carnosine
Catalase
Cell Separation
Guinea Pigs
Heart
In Vitro Techniques
Isoflurane
Membrane Potentials
Membrane Proteins
Myocardium
Myocytes, Cardiac
Patch-Clamp Techniques
Pinacidil
Potassium Channels
Reactive Oxygen Species
Sarcolemma
Superoxide Dismutase
Vasodilator Agents