Glucagon amplifies tetrodotoxin-resistant Na+ oscillations in glucose-stimulated pancreatic beta-cells.
The cytoplasmic concentration of Na+ ([Na+]i) was measured in individual mouse beta-cells with dual-wavelength microfluorometry using the indicator SBFI. The addition of 10 nM glucagon to a medium containing 11 mM glucose and 1.3 mM Ca2+ resulted in a 24% increase of [Na+]i often associated with superimposed oscillations. When replacing Ca2+ with 5 mM Sr2+, the presence of glucagon resulted in an increase of the amplitude of the [Na+]i oscillations with decrease of their frequency. Similar effects as with glucagon were obtained with 1 mM 8-Br-cAMP or 5 microM of the Ca2+ channel agonist BAY K8644. The glucose-induced oscillations of [Na+]i were resistant to 3 microM tetrodotoxin and disappeared after addition of 100 nM clonidine, 10 microM methoxyverapamil or 400 microM diazoxide. Studies of cell aggregates revealed the existence of well synchronized [Na+]i oscillations similar to those in individual beta-cells. The results provide evidence for tetrodotoxin-resistant [Na+]i rhythmicity in glucose-stimulated pancreatic beta-cells subject to regulation with cAMP.
Grapengiesser
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Department of Medical Cell Biology, Uppsala University, Sweden. Eva.Grapengiesser@medcellbiol.uu.se
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007202:Indicators and Reagents; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*
D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; D013779:Tetrodotoxin; D005934:Glucagon; D012964:Sodium; D000242:Cyclic AMP; D005947:Glucose