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
03/02/2006Pubmed ID
16508398DOI
10.1097/00000542-200603000-00018Scopus ID
2-s2.0-33645519796 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
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 ZJMESH terms used to index this publication - Major topics in bold
Adenosine DiphosphateAdenosine Triphosphate
Anesthetics, Inhalation
Animals
Ischemic Preconditioning, Myocardial
Isoflurane
Male
Myocytes, Cardiac
Pinacidil
Potassium Channels, Inwardly Rectifying
Rats
Rats, Wistar
Sarcolemma