Isoflurane activates sarcolemmal adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells: a role for protein kinase A.
Anesthesiology
; 106(5): 984-91, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17457130
ABSTRACT
BACKGROUND:
Recent evidence indicates that vascular adenosine triphosphate-sensitive potassium (K(ATP)) channels in vascular smooth muscle cells are critical in the regulation of vascular tonus under both physiologic and pathophysiologic conditions. Studies of the interaction of volatile anesthetics with vascular K(ATP) channels have been limited. In the current study, the authors investigated the molecular mechanism of isoflurane's action on vascular K(ATP) channels.METHODS:
Electrophysiologic experiments were performed using cell-attached and inside-out patch clamp techniques to monitor native vascular K(ATP) channels, and recombinant K(ATP) channels comprised of inwardly rectifying potassium channel subunits (Kir6.1) and the sulfonylurea receptor (SUR2B). Isometric tension experiments were performed in rat thoracic aortic rings without endothelium.RESULTS:
Application of isoflurane (0.5 mM) to the bath solution during cell-attached recordings induced a significant increase in K(ATP) channel activity, which was greatly reduced by pretreatment with a selective inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). In inside-out patches, isoflurane did not activate K(ATP) channels. Isoflurane significantly activated wild-type recombinant SUR2B/Kir6.1 in cell-attached patches. Isoflurane-induced activation of wild-type channels was diminished in the PKA-insensitive mutant SUR2B-T633A/Kir6.1, SUR2B-S1465A/Kir6.1, and SUR2B/Kir6.1-S385A. In addition, the authors demonstrated that isoflurane-induced PKA activation was associated with isoflurane-induced decreases in isometric tension in the rat aorta.CONCLUSION:
These results indicate that isoflurane activates K(ATP) channels via PKA activation. PKA-dependent vasodilation induced by isoflurane also was observed in isometric tension experiments. Analysis of expressed vascular-type K(ATP) channels suggested that PKA-mediated phosphorylation of both Kir6.1 and SUR2B subunits plays a pivotal role in isoflurane-induced vascular K(ATP) channel activation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Droga
/
Sarcolema
/
Canais de Potássio
/
Trifosfato de Adenosina
/
Proteínas Quinases Dependentes de AMP Cíclico
/
Anestésicos Inalatórios
/
Transportadores de Cassetes de Ligação de ATP
/
Canais de Potássio Corretores do Fluxo de Internalização
/
Isoflurano
/
Músculo Liso Vascular
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Anesthesiology
Ano de publicação:
2007
Tipo de documento:
Article