Accelerated desensitization of nicotinic receptor channels and its dependence on extracellular calcium in isolated skeletal muscles of streptozotocin-diabetic mice.
Br J Pharmacol
; 116(1): 1680-4, 1995 Sep.
Article
em En
| MEDLINE
| ID: mdl-8564237
ABSTRACT
1. To elucidate the influence of the diabetic state on desensitization of nicotinic acetylcholine (ACh) receptor channels, we investigated the time course of the decrease in amplitude of ACh potentials elicited by iontophoretic application to isolated diaphragm muscle of streptozotocin-diabetic mice. We also investigated time- and extracellular Ca(2+)-dependent changes in the channel opening frequency of ACh-activated channel currents and the involvement of protein kinases by use of the cell-attached patch clamp technique in single skeletal muscle cells. 2. When ACh potentials were evoked at 10 Hz, the decline in trains of ACh potentials was accelerated in the diabetic state. 3. The time-dependent decrease in the channel opening frequency of diabetic muscle cells was greatly accelerated compared with normal cells in 2.5 mM Ca2+ medium. 4. This accelerated decrease in channel opening frequency was restored by pretreatment with a protein kinase C inhibitor, staurosporine (10 nM) but neither a protein kinase A inhibitor, H-89 (3 microM) nor a calmodulin kinase II inhibitor, KN-62 (5 microM) were able to restore the fall in opening frequency. 5. These results demonstrate that in the diabetic state the desensitization of nicotinic ACh receptor channels may be greatly accelerated by activating protein kinase C, which is caused by an increase in the amount of available intracellular Ca2+.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Receptores Nicotínicos
/
Músculo Esquelético
/
Diabetes Mellitus Experimental
/
Canais Iônicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Japão