Modulation of calcium currents by electrical activity
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Updated: Nov 3, 2026
Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
M Li1, M Jia, R D Fields
1Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4480, USA.
Abstract:
Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures for 1-2 days produced a downregulation of voltage sensitive calcium currents, which persisted for > or = 24 h after stimulation was terminated. This regulation varied with different patterns of activation. Both the magnitude and time course of regulation of the low-threshold voltage-activated (LVA) and high-threshold voltage-activated (HVA) currents were differentially sensitive to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation (10 Hz for 0.5 s every 2 s) with an average frequency of 2.5 Hz produced significantly more downregulation of HVA currents than did the tonic 2.5-Hz stimulation. The efficacy of phasic stimulation varied inversely with the interval between bursts. Thus phasic stimulation of 10 Hz for 0.5 s but delivered every 4 s produced no effects on HVA currents. Stimulation optimal for downregulation of Ca2+ currents also produced a decreased binding by the DRG neurons of an L-type Ca2+ channel antagonist. This suggests a downregulation by electrical activity of the number of Ca2+ channels, rather than an alteration in a constant number of channels. Depression of LVA currents was produced by all stimulus patterns tested, including 0.5-Hz tonic stimulation. Chronic stimulation with a stimulation pattern that downregulated Ca2+ currents also produced a slowing of the increase in intracellular Ca2+ (as measured by Fura-2/AM) that is produced acutely by repetitive stimulation. This is consonant with earlier studies of intracellular Ca2+ concentration kinetics in growth cones.
Insights
Electrical stimulation downregulates calcium currents in dorsal root ganglion (DRG) neurons. This effect, dependent on stimulation pattern, suggests a reduction in the number of calcium channels, impacting intracellular calcium levels.
Area of Science:
- Neuroscience
- Cellular Electrophysiology
Background:
- Dorsal root ganglion (DRG) neurons play a crucial role in sensory signal transmission.
- Voltage-sensitive calcium channels are critical for neuronal excitability and neurotransmitter release.
Purpose of the Study:
- To investigate the long-term effects of electrical stimulation on calcium currents in cultured mouse DRG neurons.
- To determine how different stimulation patterns influence the downregulation of low-threshold (LVA) and high-threshold (HVA) voltage-activated calcium currents.
Main Methods:
- Cultured mouse DRG neurons were subjected to various patterns of electrical stimulation (tonic and phasic).
- Voltage-sensitive calcium currents (LVA and HVA) were measured using electrophysiology.
- Binding of an L-type calcium channel antagonist was assessed.
- Intracellular calcium levels were monitored using Fura-2/AM.
Main Results:
- Electrical activation led to a persistent downregulation of voltage-sensitive calcium currents (>24 hours post-stimulation).
- Phasic stimulation was more effective than tonic stimulation in downregulating HVA currents.
- Downregulation correlated with decreased antagonist binding, suggesting reduced calcium channel numbers.
- All tested patterns downregulated LVA currents and slowed the rise in intracellular calcium.
Conclusions:
- Electrical activity patterns differentially regulate LVA and HVA calcium currents in DRG neurons.
- The observed downregulation likely involves a decrease in the number of functional calcium channels.
- These findings have implications for understanding neuronal plasticity and calcium signaling dynamics.
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