Glucagon amplifies tetrodotoxin-resistant Na⁺ oscillations in glucose-stimulated pancreatic β-ce11s

Summary

The cytoplasmic concentration of Na⁺ ([Na]_i) was measured in individual mouse β-cells with dual-wavelength microfluorometry using the indicator SBFI. The addition of 10 nM glucagon to a medium containing II 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 μM of the Ca²⁺ channel agonist BAY K8644. The glucose-induced oscillations of [Na⁺]_i were resistant to 3 μM tetrodotoxin and disappeared after addition of 100 nM clonidine, 10 μM methoxyverapamil or 400 μM diazoxide. Studies of cell aggregates revealed the existence of well synchronized [Na⁺]_i, oscillations similar to those in individual β-cells. The results provide evidence for tetrodotoxin- resistant [Na⁺]_i rhythmicity in glucose-stimulated pancreatic β-cells subject to regulation with cAMP.

Key words

Cyclic AMP - Glucose-induced oscillation - SBFI