Nerve growth factor increases L-type calcium current in pancreatic β cells in culture

We analyzed the effect of culturing adult rat beta cells with NGF2.5 S for 5 to 7 days on macroscopic barium current (I-Ba], and determined the role of Na and Ca channels on neurite-like process extension induced by NGF and dbcAMP, and by KCl depolarization. After five days in culture with 2.5S NGF, beta cells exhibit a 102% increase in I-Ba. density. This effect is on L-type calcium channels because most of the current is blocked by nifedipine. The application of NGF for 5 minutes to the cells deprived of the trophic factor for 24 hr further increases I-Ba current by 91%. These results suggest that the trophic factor regulates I-Ba by two different mechanisms, a) an increase in channel density and b) a rapid modulation of the channels already present in the membrane. Finally, we found that ion-channel activity modifies the growth of neurite-like processes. After 2 weeks in culture with high KCl, almost 14% of beta cells extend neurite-like processes and the most impressive effect is observed in the presence of KCl, NGF, and dbcAMP simultaneously, where nearly 60% of the cells extend neurite-like processes. Tetrodotoxin and nifedipine reduce the morphological changes induced by these agents.