Postnatal Development and Activation of L-Type Ca²⁺ Currents in Locus Ceruleus Neurons: Implications for a Role for Ca²⁺ in Central Chemosensitivity

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.