Nerve growth factor increases L-type calcium current in pancreatic beta 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 KCI 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.
Rosenbaum
T
T
Dept Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Coyoacán, Mexico City, DF, Mexico.
Castañares
D T
DT
López-Valdés
H E
HE
Hiriart
M
M
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D013779:Tetrodotoxin; D003994:Bucladesine; D011189:Potassium Chloride; D020932:Nerve Growth Factor; D009543:Nifedipine