Modulation of the effect of acetylcholine on insulin release by the membrane potential of B cells

Journal Article · Fri May 01 04:00:00 EDT 1987 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-120-5-1765· OSTI ID:6468113

Hermans, M P; Schmeer, W; Henquin, J C

Mouse islets were used to test the hypothesis that the B cell membrane must be depolarized for acetylcholine to increase insulin release. The resting membrane potential of B cells (at 3 mM glucose) was slightly decreased (5 mV) by acetylcholine, but no electrical activity appeared. This depolarization was accompanied by a Ca-independent acceleration of /sup 86/Rb and /sup 45/Ca efflux but no insulin release. When the B cell membrane was depolarized by a stimulatory concentration of glucose (10 mM), acetylcholine potentiated electrical activity, accelerated /sup 86/Rb and /sup 45/Ca efflux, and increased insulin release. This latter effect, but not the acceleration of /sup 45/Ca efflux, was totally dependent on extracellular Ca. If glucose-induced depolarization of the B cell membrane was prevented by diazoxide, acetylcholine lost all effects but those produced at low glucose. In contrast, when the B cell membrane was depolarized by leucine or tolbutamide (at 3 mM glucose), acetylcholine triggered a further depolarization with appearance of electrical activity, accelerated /sup 86/Rb and /sup 45/Ca efflux, and stimulated insulin release. Acetylcholine produced similar effects (except for electrical activity) in the presence of high K or arginine which, unlike the above test agents, depolarize the B cell membrane by a mechanism other than a decrease in K+ permeability. Omission of extracellular Ca abolished the releasing effect of acetylcholine under all conditions but only partially decreased the stimulation of /sup 45/Ca efflux. The results show thus that acetylcholine stimulation of insulin release does not result from mobilization of cellular Ca but requires that the B cell membrane be sufficiently depolarized to reach the threshold potential where Ca channels are activated. This may explain why acetylcholine alone does not initiate release but becomes active in the presence of a variety of agents.

• Research Organization: Univ. of Louvain, Faculty of Medicine, Brussels, Belgium
• OSTI ID: 6468113
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 5; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
ALDEHYDES
ALKALI METAL ISOTOPES
ALKALI METALS
ALKALINE EARTH ISOTOPES
AMINES
AMINO ACIDS
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
ARGININE
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CALCIUM 45
CALCIUM ISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
DAYS LIVING RADIOISOTOPES
DRUGS
ELEMENTS
ESTERS
EVEN-ODD NUCLEI
GLUCOSE
HEXOSES
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LEUCINE
MAMMALS
MEMBRANE TRANSPORT
MEMBRANES
METALS
MICE
MINUTES LIVING RADIOISOTOPES
MONOSACCHARIDES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PEPTIDE HORMONES
POTASSIUM
QUATERNARY COMPOUNDS
RADIOISOTOPES
RESPONSE MODIFYING FACTORS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
SACCHARIDES
VERTEBRATES