Involvement of 3Na+/2K+ ATP-ase and Pi-3 kinase in the response of skeletal muscle ATP-sensitive K+ channels to insulin.
Neuromuscul Disord
; 13(9): 712-9, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14561494
ABSTRACT
The modulation of ATP-sensitive K+ channel (K(ATP)) by insulin plays a role in neuromuscular disorders associated to altered K+ homeostasis. However, the mechanisms by which insulin modulates K(ATP) channels are not known. Here, the insulin-dependent 3Na+/2K+ ATP-ase and Pi-3 kinase pathways were explored by using patch-clamp techniques. High and low affinity inhibition of K(ATP) channels by ouabain was observed in the insulin-stimulated and resting fibers, respectively. The 9A5 antibody directed against the alpha1-subunit of the pump inhibited the K(ATP) channel in the resting fibers but fails to inhibit it in the insulin-stimulated fibers. In contrast, the RT2NKATPabr, an alpha2-subunit specific antibody, inhibited the K(ATP) channels in the insulin-stimulated fibers failing to inhibit it in the resting fibers. The insulin-dependent stimulation of K(ATP) channel was prevented by Pi-3 kinase inhibitors Wortmannin and LY294002. In conclusion, insulin stimulating the 3Na+/2K+ ATP-ase activates K(ATP) channels through a membrane-delimited interaction thus controlling the K+ homeostasis. The Pi-3 kinase is the intracellular insulin signal linking the glucose homeostasis to the K(ATP) channel.
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Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
ATPase Trocadora de Sódio-Potássio
/
Músculo Esquelético
/
Fosfatidilinositol 3-Quinases
/
Hipoglicemiantes
/
Insulina
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article