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

Imber AN, Putnam RW. Postnatal development and activation of L-type Ca currents in locus ceruleus neurons: implications for a role for Ca in central chemosensitivity. J Appl Physiol 112: 1715–1726, 2012. First published March 8, 2012; doi:10.1152/japplphysiol.01585.2011.— Little is known about the role of Ca 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 channel inhibition and are activated by increased CO2/H . Spikes appear to arise from L-type Ca channels on the soma whereas oscillations arise from L-type Ca 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 Ca 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 currents in LC neurons arise from channel populations that reside in different regions of the neuron, 2) these L-type Ca currents undergo significant postnatal development, and 3) the activity of these L-type Ca currents is activated by increased CO2 through a HCO3 -dependent mechanism. Thus the activity of L-type Ca 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.