Phasic and tonic modes of depolarization-exocytosis coupling in beta-cells of porcine islets of Langerhans.

In response to depolarizations that open voltage dependent Ca2+ channels single porcine beta-cells display heterogeneous time courses of exocytosis. Some cells display phasic exocytosis that is triggered by individual or short burst of action potentials typically characteristic of glucose-induced electrical activity or brief voltage clamp depolarization. Other cells, singularly or additionally, display tonic exocytosis that (i) is triggered during prolonged (up to seconds-long) depolarizations to voltages (-30 to -20 mV), and (ii) coincides with rises in global cytosolic [Ca2+] >500 nM. We suggest that tonic exocytosis (i) likely results from a recently described pool of granules that is more Ca2+ sensitive and less co-localized with voltage-sensitive Ca2+ entry channels than that contributing to phasic exocytosis and (ii) helps tune exocytosis to glucose-induced electrical activity when the latter consists of spike activity followed by intervals of plateau depolarization to nearly -20 mV.