title: Mechanisms of Na+ and Ca2+ influx into respiratory neurons during hypoxia.
abstract: Changes in intracellular Na+ and Ca2+ in inspiratory neurons of neonatal mice were examined by using ion-selective fluorescent indicator dyes SBFI and fura-2, respectively. Both [Na+]i and [Ca2+]i signals showed rhythmic elevations, correlating with the inspiratory motor output. Brief (2-3 min) hypoxia, induced initial potentiation of rhythmic transients followed by their depression. During hypoxia, the basal [Na+]i and [Ca2+]i levels slowly increased, reflecting development of an inward current (Im). By antagonizing specific mechanisms of Na+ and Ca2+ transport we found that increases in [Na+]i, [Ca2+]i and Im due to hypoxia are suppressed by CNQX, nifedipine, riluzole and flufenamic acid, indicating contribution of AMPA/kainate receptors, persistent Na+ channels, L-type Ca2+ channels and Ca2+-sensitive non-selective cationic channels, respectively. The blockers decreased also the amplitude of the inspiratory bursts. Modification of mitochondrial properties with FCCP and cyclosporine A decreased [Ca2+]i elevations due to hypoxia by about 25%. After depletion of internal Ca2+ stores with thapsigargin, the blockade of NMDA receptors, Na+/K+ pump, Na+/H+ and Na+/Ca2+ exchange, the hypoxic response was not changed. We conclude that slow [Na+]i and [Ca2+]i increases in inspiratory neurons during hypoxia are caused by Na+ and Ca2+ entry due to combined activation of persistent Na+ and L-type Ca2+ channels and AMPA/kainate receptors.
authors.affiliation: Department of Neuro- and Sensory Physiology, Georg-August-University, Humboldtallee 23, Göttingen 37073, Germany. slm@ukps.gwdg.de
authors.forename: S L
authors.initials: SL
authors.lastname: Mironov
authors.forename: K
authors.initials: K
authors.lastname: Langohr
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D015220:Calcium Channels; D015222:Sodium Channels; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D009543:Nifedipine