Mechanisms of Na+ and Ca2+ influx into respiratory neurons during hypoxia |
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Authors: | Mironov S L Langohr K |
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Affiliation: | Department of Neuro- and Sensory Physiology, Georg-August-University, Humboldtallee 23, G?ttingen 37073, Germany. slm@ukps.gwdg.de |
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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. |
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Keywords: | Inspiratory neuron Hypoxia Intracellular Na+ Intracellular Ca2+ AMPA/Kainate receptor Persistent Na+ channel Ca2+-sensitive non-selective cationic channel L-type Ca2+ channel |
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