title: Characteristics of the hypoosmosis-induced calcium response in isolated nerve terminals of rat brain.
abstract: BACKGROUND
  Cerebral edema contributes significantly to morbidity and death in many common neurological disorders. Ca2+ ions play a important role in the development of pathophysiological reactions in nerve cells. The aim of our research was to elucidate the mechanism of the osmotically-induced entrance of Ca2+ into nerve terminals (synaptosomes) and to estimate the involvement of endoplasmic reticulum Ca2+ stores in intrasynaptosomal Ca2+-dependent processes in hypoosmotic swelling.
  
  
  METHODS
  Synaptosomes were isolated from rat brains. The rates of Ca2+ uptake were determined using 45Ca2+ as a radiotracer. Intracellular Ca2+ measurements were performed using Fura-2 as a cell calcium indicator.
  
  
  RESULTS
  Entry into synaptosomes in hypotonic medium (230 mOsm) of osmosis-induced Ca2+ (45 Ca2+) was reduced by verapamil, Cd2+ or genistein to 50-60% of baseline. NEM and PCMB inhibit 45Ca2+ uptake. Swelling of synaptosomes is coupled with increased tyrosine kinase activity and oxidation of SH-groups of cysteine residues of the membrane proteins involved in Ca2+ transport. These membrane processes probably influence the properties of voltage-dependent L-type Ca2+ channels, which increase their conductivity to Ca2+. Activation of RyR- and Ins(1,4,5,)P3-stores were recorded. It was shown that the Ins(1,4,5,)P3-stores are a major source of the increase in [Ca2+]i in the cytoplasm with swelling of the synaptosomes.
  
  
  CONCLUSIONS
  Osmotic swelling of synaptosomes leads to Ca2+ accumulation by intrasynaptosomal mitochondria. Excess Ca2+ ions stored in mitochondria inhibit oxidative phosphorylation. This causes an irreversible reduction in the energy status of nerve terminals, which can initiate pathophysiological processes in nerve cells.
authors.affiliation: Institute of Photobiology, National Academy of Sciences of Belarus, Minsk, Belarus.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Levko
authors.forename: Anatoly A
authors.initials: AA
authors.lastname: Rakovich
authors.forename: Svetlana G
authors.initials: SG
authors.lastname: Samoilenko
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Konev
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004553:Electric Conductivity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016257:Fura-2; D019833:Genistein / Q000494:pharmacology; D007038:Hypotonic Solutions; D017136:Ion Transport / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009997:Osmotic Pressure / Q000187:drug effects*; D010085:Oxidative Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007038:Hypotonic Solutions; D002104:Cadmium; D000255:Adenosine Triphosphate; D014700:Verapamil; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D016257:Fura-2