Improvement of the metabolic status recovers cardiac potassium channel synthesis in experimental diabetes.
Acta Physiol (Oxf)
; 207(3): 447-59, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23181465
ABSTRACT
AIMS:
The fast transient outward current, I(to,fast) , is the most extensively studied cardiac K(+) current in diabetic animals. Two hypotheses have been proposed to explain how type-1 diabetes reduces this current in cardiac muscle. The first one is a deficiency in channel expression due to a defect in the trophic effect of insulin. The second one proposes flawed glucose metabolism as the cause of the reduced I(to,fast) . Moreover, little information exists about the effects and possible mechanisms of diabetes on the other repolarizing currents of the human heart I(to,slow) , I(Kr) , I(Ks) , I(Kur) , I(Kslow) and I(K1) .METHODS:
We recorded cardiac action potentials and K(+) currents in ventricular cells isolated from control and streptozotocin- or alloxan-induced diabetic mice and rabbits. Channel protein expression was determined by immunofluorescence.RESULTS:
Diabetes reduces the amplitude of I(to,fast) , I(to,slow) and I(Kslow) , in ventricular myocytes from mouse and rabbit, with no effect on I(ss) , I(Kr) or I(K1) . The absence of changes in the biophysical properties of the currents and the immunofluorescence experiments confirmed the reduction in channel protein synthesis. Six-hour incubation of myocytes with insulin or pyruvate recovered current amplitudes and fluorescent staining. The activation of AMP-K reduced the same K(+) currents in healthy myocytes and prevented the pyruvate-induced current recovery.CONCLUSION:
Diabetes reduces K(+) current densities in ventricular myocytes due to a defect in channel protein synthesis. Activation of AMP-K secondary to deterioration in the metabolic status of the cells is responsible for K(+) channel reductions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicemia
/
Canais de Potássio
/
Miócitos Cardíacos
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Diabetes Mellitus Experimental
/
Metabolismo Energético
/
Hipoglicemiantes
/
Insulina
Limite:
Animals
Idioma:
En
Revista:
Acta Physiol (Oxf)
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article