ISSN:
1432-1424
Keywords:
Muscarinic agonist
;
β-cell electrical activity
;
Insulin secretion
;
K+-permeability
;
CRAC
;
Charybdotoxin
;
Mouse
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract The effects of the muscarinic agonist oxotremorine-m (oxo-m) on insulin secretion, K+-permeability and electrical activity from isolated mouse pancreatic islets were studied. Oxo-m potentiated glucose-induced insulin secretion in a dose-dependent manner, saturating at ca. 10 μm. At 11.2 mm glucose, oxo-m (0.1 and 10 μm) had two distinct effects on β-cell electrical activity. Both concentrations increased the steadystate burst frequency, however, at 10 μm an initial and transient polarization was measured, and the subsequent activity was accompanied by a slight depolarization. The polarizing effect of oxo-m was almost completely suppressed by charybdotoxin (ChTX), a blocker of the large conductance (maxi) [Ca2+] i -activated potassium channel (K(Ca)). In the presence of 11.2 mm glucose, oxo-m (50 μm) provoked a significant and transient increase in the 86Rb efflux from perifused islets. This effect was inhibited by ChTX. ChTX also potentiated oxo-m stimulated insulin secretion in the presence of glucose. Finally, the balance between the polarizing and depolarizing effects of oxo-m was variable in different islets and depended on glucose concentration. Insulin secretion stimulated by oxo-m in the presence of glucose was more closely correlated to the agonist induced increase in burst frequency than to an increase in plateau fraction. We conclude that muscarinic stimulation has at least two effects on β-cell electrical activity, an initial hyperpolarization, owing to activation of K(Ca) channels, followed by depolarization and high-frequency bursts, proposed to reflect the activation of a current sensitive to the depletion of intracellular Ca2+ stores (CRAC).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00207273
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