Postnatal Development and Activation of L-Type Ca\u3csup\u3e2+\u3c/sup\u3e Currents in Locus Ceruleus Neurons: Implications for a Role for Ca\u3csup\u3e2+\u3c/sup\u3e in Central Chemosensitivity

摘要

Little is known about the role of Ca2+ 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 Ca2+channel inhibition and are activated by increased CO2/H+. Spikes appear to arise from L-type Ca2+ channels on the soma whereas oscillations arise from L-type Ca2+ channels that are distal to the soma. In HEPES-buffered solution (nominal absence of CO2/HCO3−), acidification does not activate either oscillations or spikes. When CO2 is increased while extracellular pH is held constant by elevated HCO3−, both oscillation and spike frequency increase. Furthermore, plots of both oscillation and spike frequency vs. intracellular [HCO3−]show a strong linear correlation. Increased frequency of TTX-insensitive spikes is associated with increases in intracellular Ca2+ concentrations. Finally, both the appearance and frequency of TTX-insensitive spikes and oscillations increase over postnatal agesday 3–16. Our data suggest that 1) L-type Ca2+ currents in LC neurons arise from channel populations that reside in different regions of the neuron, 2) these L-type Ca2+ currents undergo significant postnatal development, and 3) the activity of these L-type Ca2+ currents is activated by increased CO2 through a HCO3−-dependent mechanism. Thus the activity of L-type Ca2+ 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.