alpha-Latrotoxin increases spontaneous and depolarization-evoked exocytosis from pancreatic islet beta-cells.
J Physiol
; 565(Pt 3): 783-99, 2005 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-15760942
alpha-Latrotoxin (alpha-LT), a potent excitatory neurotoxin, increases spontaneous, as well as action potential-evoked, quantal release at nerve terminals and increases hormone release from excitable endocrine cells. We have investigated the effects of alpha-LT on single human, mouse and canine beta-cells. In isolated and combined measurements, alpha-LT, at nanomolar concentrations, induces: (i) rises in cytosolic Ca(2+), into the micromolar range, that are dependent on extracellular Ca(2+); (ii) large conductance non-selective cation channels; and (iii) Ca(2+)-dependent insulin granule exocytosis, measured as increases in membrane capacitance and quantal release of preloaded serotonin. Furthermore, at picomolar concentrations, alpha-LT potentiates depolarization-induced exocytosis often without evidence of inducing channel activity or increasing cytosolic Ca(2+). These results strongly support the hypothesis that alpha-LT, after binding to specific receptors, has at least two complementary modes of action on excitable cells. (i) alpha-LT inserts into the plasma membrane to form Ca(2+) permeable channels and promote Ca(2+) entry thereby triggering Ca(2+)-dependent exocytosis in unstimulated cells. (ii) At lower concentrations, where its channel forming activity is hardly evident, alpha-LT augments depolarization-evoked exocytosis probably by second messenger-induced enhancement of the efficiency of the vesicle recruitment or vesicle fusion machinery. We suggest that both modes of action enhance exocytosis from a newly described highly Ca(2+)-sensitive pool of insulin granules activated by global cytosolic Ca(2+) concentrations in the range of approximately 1 microm.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Venenos de Araña
/
Islotes Pancreáticos
/
Exocitosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Physiol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido