A store-operated mechanism determines the activity of the electrically excitable glucagon-secreting pancreatic alpha-cell.
Cell Calcium
; 35(4): 357-65, 2004 Apr.
Article
em En
| MEDLINE
| ID: mdl-15036952
ABSTRACT
The glucagon-releasing pancreatic alpha-cells are electrically excitable cells but the signal transduction leading to depolarization and secretion is not well understood. To clarify the mechanisms we studied [Ca(2+)](i) and membrane potential in individual mouse pancreatic alpha-cells using fluorescent indicators. The physiological secretagogue l-adrenaline increased [Ca(2+)](i) causing a peak, which was often followed by maintained oscillations or sustained elevation. The early effect was due to mobilization of Ca(2+) from the endoplasmic reticulum (ER) and the late one to activation of store-operated influx of the ion resulting in depolarization and Ca(2+) influx through voltage-dependent L-type channels. Consistent with such mechanisms, the effects of adrenaline on [Ca(2+)](i) and membrane potential were mimicked by inhibitors of the sarco(endo)plasmic reticulum Ca(2+) ATPase. The alpha-cells express ATP-regulated K(+) (K(ATP)) channels, whose activation by diazoxide leads to hyperpolarization. The resulting inhibition of the voltage-dependent [Ca(2+)](i) response to adrenaline was reversed when the K(ATP) channels were inhibited by tolbutamide. However, tolbutamide alone rarely affected [Ca(2+)](i), indicating that the K(ATP) channels are normally closed in mouse alpha-cells. Glucose, which is the major physiological inhibitor of glucagon secretion, hyperpolarized the alpha-cells and inhibited the late [Ca(2+)](i) response to adrenaline. At concentrations as low as 3mM, glucose had a pronounced stimulatory effect on Ca(2+) sequestration in the ER amplifying the early [Ca(2+)](i) response to adrenaline. We propose that adrenaline stimulation and glucose inhibition of the alpha-cell involve modulation of a store-operated current, which controls a depolarizing cascade leading to opening of L-type Ca(2+) channels. Such a control mechanism may be unique among excitable cells.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glucagon
/
Canais de Cálcio
/
Cálcio
/
Ilhotas Pancreáticas
/
Retículo Endoplasmático
/
Potenciais da Membrana
Limite:
Animals
Idioma:
En
Revista:
Cell Calcium
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Suécia