Postnatal development and activation of L-type Ca2+ currents in locus ceruleus neurons: implications for a role for Ca2+ in central chemosensitivity

J Appl Physiol (1985). 2012 May;112(10):1715-26. doi: 10.1152/japplphysiol.01585.2011. Epub 2012 Mar 8.


Little is known about the role of Ca(2+) in central chemosensitive signaling. We use electrophysiology to examine the chemosensitive responses of tetrodotoxin (TTX)-insensitive oscillations and spikes in neurons of the locus ceruleus (LC), a chemosensitive region involved in respiratory control. We show that both TTX-insensitive spikes and oscillations in LC neurons are sensitive to L-type Ca(2+) channel inhibition and are activated by increased CO(2)/H(+). Spikes appear to arise from L-type Ca(2+) channels on the soma whereas oscillations arise from L-type Ca(2+) channels that are distal to the soma. In HEPES-buffered solution (nominal absence of CO(2)/HCO(3)(-)), acidification does not activate either oscillations or spikes. When CO(2) is increased while extracellular pH is held constant by elevated HCO(3)(-), both oscillation and spike frequency increase. Furthermore, plots of both oscillation and spike frequency vs. intracellular [HCO(3)(-)]show a strong linear correlation. Increased frequency of TTX-insensitive spikes is associated with increases in intracellular Ca(2+) concentrations. Finally, both the appearance and frequency of TTX-insensitive spikes and oscillations increase over postnatal ages day 3-16. Our data suggest that 1) L-type Ca(2+) currents in LC neurons arise from channel populations that reside in different regions of the neuron, 2) these L-type Ca(2+) currents undergo significant postnatal development, and 3) the activity of these L-type Ca(2+) currents is activated by increased CO(2) through a HCO(3)(-)-dependent mechanism. Thus the activity of L-type Ca(2+) channels is likely to play a role in the chemosensitive response of LC neurons and may underlie significant changes in LC neuron chemosensitivity during neonatal development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Bicarbonates / metabolism
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism*
  • Calcium Signaling* / drug effects
  • Carbon Dioxide / metabolism
  • Chemoreceptor Cells / drug effects
  • Chemoreceptor Cells / metabolism*
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Ion Channel Gating* / drug effects
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / growth & development
  • Locus Coeruleus / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Respiration
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Time Factors


  • Bicarbonates
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Sodium Channel Blockers
  • Carbon Dioxide
  • Tetrodotoxin
  • Nifedipine
  • Calcium