title: Postnatal development and activation of L-type Ca2+ currents in locus ceruleus neurons: implications for a role for Ca2+ in central chemosensitivity.
abstract: 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.
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435, USA.
authors.forename: Ann N
authors.initials: AN
authors.lastname: Imber
authors.forename: Robert W
authors.initials: RW
authors.lastname: Putnam
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001639:Bicarbonates; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026941:Sodium Channel Blockers; D002245:Carbon Dioxide; D013779:Tetrodotoxin; D009543:Nifedipine; D002118:Calcium