Dihydropyridine-sensitive and -insensitive voltage-operated calcium channels participate in the control of glucose-induced insulin release from human pancreatic beta cells

Calcium ion entry through voltage-operated calcium channels is a crucial step in the coupling of beta cell depolarization with insulin secretion. Various calcium channel subtypes have been shown to be coexpressed in single neurons and endocrine cells. Using the patch-clamp technique, we investigated the biophysical and pharmacological properties of calcium channels in freshly dispersed human pancreatic beta cells. Both low and high voltage activated currents were expressed, the two current types being easily distinguishable on the basis of biophysical criteria. The high voltage activated currents were not homogeneous: one component was affected by the dihydropyridine antagonist nitrendipine and the agonist Bay-K-8644; the other was insensitive to both dihydropyridines and omega-conotoxin GVIA. In Line with this pharmacology, nitrendipine reduced and Bay-K-8644 increased glucose-induced insulin secretion from perifused human islets, whereas omega-conotoxin GVIA had no effect. However, about 20% of the glucose-induced insulin release was found to be resistant to high nitrendipine concentrations. These data show that human pancreatic beta cells express heterogeneous voltage-operated calcium channels, only one of which is dihydropyridine-sensitive (L type) The L type channels are clearly involved in the control of insulin secretion, but our data suggest that dihydropyridine- and omega-conotoxin GVIA-insensitive channels may also play a role in the stimulus-secretion coupling of human beta cells.