title: Cytosolic calcium regulation in rat afferent vagal neurons during anoxia.
abstract: Sensory neurons are able to detect tissue ischaemia and both transmit information to the brainstem as well as release local vasoactive mediators. Their ability to sense tissue ischaemia is assumed to be primarily mediated through proton sensing ion channels, lack of oxygen however may also affect sensory neuron function. In this study we investigated the effects of anoxia on isolated capsaicin sensitive neurons from rat nodose ganglion. Acute anoxia triggered a reversible increase in [Ca2+]i that was mainly due to Ca2+-efflux from FCCP sensitive stores and from caffeine and CPA sensitive ER stores. Prolonged anoxia resulted in complete depletion of ER Ca2+-stores. Mitochondria were partially depolarised by acute anoxia but mitochondrial Ca2+-uptake/buffering during voltage-gated Ca2+-influx was unaffected. The process of Ca2+-release from mitochondria and cytosolic Ca2+-clearance following Ca2+ influx was however significantly slowed. Anoxia was also found to inhibit SERCA activity and, to a lesser extent, PMCA activity. Hence, anoxia has multiple influences on [Ca2+]i homeostasis in vagal afferent neurons, including depression of ATP-driven Ca2+-pumps, modulation of the kinetics of mitochondrial Ca2+ buffering/release and Ca2+-release from, and depletion of, internal Ca2+-stores. These effects are likely to influence sensory neuronal function during ischaemia.
authors.affiliation: Department of Anaesthesia, Intensive Care Medicine, Pain Therapy, Justus-Liebig-University Giessen, Rudolf-Buchheim-Str. 7, D-35392 Giessen, Germany. Electronic address: michael.henrich@anatomie.med.uni-giessen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Henrich
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Buckler
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
chemical_list: D002110:Caffeine; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002211:Capsaicin; D002118:Calcium
keywords: Anoxia; Calcium; ER; Mitochondria; SERCA; Vagal neurons