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Published on: February 18, 2020
Voltage-sensitive calcium currents are acutely increased by nerve growth factor in PC12 cells
1Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Journal of Neurophysiology
|December 22, 1999
Summary
Nerve growth factor (NGF) significantly boosts calcium currents in PC12 cells via L-type channels, a process involving kinase C. This finding highlights neurotrophins
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), play critical roles in neuronal development, survival, and function.
- Calcium ions (Ca2+) are essential second messengers involved in numerous cellular processes, including neurotransmitter release and neuronal plasticity.
- PC12 cells are a widely used neuronal model system for studying cellular signaling pathways and the effects of neurotrophic factors.
Purpose of the Study:
- To investigate the effects of NGF and BDNF on whole-cell calcium currents in PC12 cells.
- To elucidate the signaling pathways, including kinase C, involved in neurotrophin-induced calcium current modulation.
- To assess the role of PC12 cells as a model for studying neurotrophin actions on calcium uptake.
Main Methods:
- Whole-cell calcium currents were recorded from PC12 cells using the perforated patch-clamp technique.
- Currents were evoked by step depolarization from a holding potential of -90 mV.
- The effects of NGF, BDNF, K-252a, nifedipine, and kinase C inhibition/down-regulation on calcium currents were examined.
Main Results:
- NGF rapidly increased calcium currents through L-type calcium channels by over 75% within 3-5 minutes.
- This NGF-induced increase was attenuated by K-252a, nifedipine, and inhibition or down-regulation of kinase C.
- BDNF also enhanced calcium currents, though to a lesser extent than NGF.
- The results suggest that calcium current modulation by neurotrophins is linked to the activation of either high- or low-affinity NGF receptors.
Conclusions:
- NGF and BDNF modulate calcium currents in PC12 cells, indicating a role for calcium signaling in neurotrophin action.
- Kinase C and L-type calcium channels are key mediators in the rapid effects of NGF on calcium influx.
- PC12 cells serve as a valuable model for exploring the impact of neurotrophins on calcium uptake, relevant to both short-term (neurotransmitter release) and long-term (neuronal survival) neuronal functions.
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