Faculty Collaboration Database

Impact of in vivo preconditioning by isoflurane on adenosine triphosphate-sensitive potassium channels in the rat heart: lasting modulation of nucleotide sensitivity during early memory period. Anesthesiology 2006 Mar;104(3):503-10

Date

03/02/2006

Pubmed ID

16508398

DOI

10.1097/00000542-200603000-00018

Scopus ID

2-s2.0-33645519796 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

BACKGROUND: The early memory of anesthetic-induced preconditioning (APC) is a period when myocardial protection continues even after removal of the anesthetic. Because adenosine triphosphate-sensitive potassium (KATP) channels are important mediators of APC, the authors investigated the hypothesis that the memory involves channel priming by isoflurane via a long-term modulation of the sensitivity to intracellular adenosine nucleotides.

METHODS: Ventricular cardiomyocytes were obtained from the rat hearts after 30 min in vivo APC with 1.4% isoflurane and from control non-APC rat hearts. Whole cell and excised inside-out patch clamp techniques were used to study the sarcolemmal KATP channel. Membrane expression of KATP channel proteins, the pore-forming inward rectifier Kir6.2, and the regulatory sulfonylurea receptor SUR2A were assessed in APC and non-APC hearts by Western blotting.

RESULTS: Activation of whole cell KATP current by isoflurane was enhanced after in vivo APC. At the single-channel level, this was paralleled by a 12-fold decrease in adenosine 5'-triphosphate sensitivity and a 3-fold decrease in adenosine 5'-diphosphate sensitivity, without changing the probability of channel opening or single-channel conductance. The membrane expression of Kir6.2 and SUR2A subunits was not altered by in vivo APC. A direct in vitro application of isoflurane to excised membrane patches increased the channel open probability and produced a 4-fold decrease in adenosine 5'-triphosphate sensitivity only of channels in non-APC myocytes.

CONCLUSIONS: In vivo APC by isoflurane decreases sensitivity of the sarcolemmal KATP channel to inhibition by adenosine 5'-triphosphate and decreases adenosine 5'-diphosphate sensitivity. These effects persist even after discontinuation of the anesthetic, suggesting a possible novel factor that may contribute to the mechanism of early memory of APC.

Author List

Stadnicka A, Marinovic J, Bienengraeber M, Bosnjak ZJ

Author

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin

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

Adenosine Diphosphate
Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Myocytes, Cardiac
Pinacidil
Potassium Channels, Inwardly Rectifying
Rats
Rats, Wistar
Sarcolemma