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Neuronal differentiation of Ca2+ channel by nerve growth factor
Abstract:
The inhibitory effect of nicardipine, a potent Ca2+ channel blocker in muscular cells, on the Ca2+ channel of clonal rat pheochromocytoma cells (PC12h) and cultured rat adrenal medullary cells was studied during the neuronal differentiation mediated by nerve growth factor (NGF). Nicardipine at nM-order concentrations suppressed the high-K+-evoked, Ca2+-dependent release of preloaded [3H]norepinephrine from PC12h cells and adrenal medullary cells, whereas it scarcely inhibited the release from the cultured rat brainstem cells. The inhibitory actions of nicardipine on both PC12h and newborn rat adrenal medullary cells were significantly decreased after these cells were cultured in the presence of NGF. These results suggest that the changes in Ca2+ channel are accompanied by the neuronal differentiation mediated by NGF.
Insights
Nicardipine, a calcium channel blocker, inhibits neurotransmitter release. Nerve growth factor (NGF) reduces nicardipine
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Calcium channels play a crucial role in neuronal function and neurotransmitter release.
- Neuronal differentiation, mediated by nerve growth factor (NGF), involves significant cellular changes.
- Understanding how drugs interact with calcium channels during differentiation is vital.
Purpose of the Study:
- To investigate the effect of nicardipine, a calcium channel blocker, on neurotransmitter release.
- To examine how neuronal differentiation induced by NGF alters the sensitivity to nicardipine.
- To explore the role of calcium channels in NGF-mediated neuronal differentiation.
Main Methods:
- Utilized clonal rat pheochromocytoma cells (PC12h) and cultured rat adrenal medullary cells.
- Studied the high-K+-evoked, Ca2+-dependent release of [3H]norepinephrine.
- Assessed the effects of nicardipine before and after NGF-induced neuronal differentiation.
Main Results:
- Nicardipine (nM concentrations) suppressed norepinephrine release from PC12h and adrenal medullary cells.
- This inhibitory effect was significantly reduced in cells cultured with NGF.
- Minimal inhibition was observed in cultured rat brainstem cells, indicating cell-type specificity.
Conclusions:
- Neuronal differentiation mediated by NGF alters the function of calcium channels.
- The reduced sensitivity to nicardipine suggests changes in calcium channel properties during differentiation.
- These findings highlight the dynamic nature of calcium channels during neuronal development.