Activation of nuclear calcium dynamics by synaptic stimulation in cultured cortical neurons

J Neurochem. 1999 Sep;73(3):1075-83. doi: 10.1046/j.1471-4159.1999.0731075.x.


L-type voltage-sensitive Ca2+ channels (VSCCs) are enriched on the neuronal soma and trigger gene expression during synaptic activity. To understand better how these channels regulate somatic and nuclear Ca2+ dynamics, we have investigated Ca2+ influx through L-type VSCCs following synaptic stimulation, using the long-wavelength Ca2+ indicator fluo-3 combined with laser scanning confocal microscopy. Single synaptic stimuli resulted in rapid Ca2+ transients in somatic cytoplasmic compartments (<5 ms rise time). Nuclear Ca2+ elevations lagged behind cytoplasmic levels by approximately 60 ms, consistent with a dependence on diffusion from a cytoplasmic source. Pharmacological experiments indicated that L-type VSCCs mediated approximately 50% of the nuclear and somatic (cytoplasmic) Ca2+ elevation in response to strong synaptic stimulation. In contrast, relatively weak excitatory postsynaptic potentials (EPSPs; approximately 15 mV) or single action potentials were much less effective at activating L-type VSCCs. Antagonist experiments indicated that activation of the NMDA-type glutamate receptor leads to a long-lasting somatic depolarization necessary to activate L-type VSCCs effectively during synaptic stimuli. Simulation of action potential and somatic EPSP depolarization using voltage-clamp pulses indicated that nuclear Ca2+ transients mediated by L-type VSCCs were produced by sustained depolarization positive to -25 mV. In the absence of synaptic stimulation, action potential stimulation alone led to elevations in nuclear Ca2+ mediated by predominantly non-L-type VSCCs. Our results suggest that action potentials, in combination with long-lived synaptic depolarizations, facilitate the activation of L-type VSCCs. This activity elevates somatic Ca2+ levels that spread to the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / physiology
  • Calcium Channels, L-Type
  • Cell Nucleus / physiology*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology*
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • Kinetics
  • Microscopy, Confocal
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / physiology*


  • Calcium Channels
  • Calcium Channels, L-Type
  • Receptors, N-Methyl-D-Aspartate
  • Calcium