title: Two mechanisms that raise free intracellular calcium in rat hippocampal neurons during hypoosmotic and low NaCl treatment.
abstract: Previous studies have shown that exposing hippocampal slices to low osmolarity (pi(o)) or to low extracellular NaCl concentration ([NaCl](o)) enhances synaptic transmission and also causes interstitial calcium ([Ca(2+)](o)) to decrease. Reduction of [Ca(2+)](o) suggests cellular uptake and could explain the potentiation of synaptic transmission. We measured intracellular calcium activity ([Ca(2+)](i)) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices, lowering pi(o) by approximately 70 mOsm caused "resting" [Ca(2+)](i) as well as synaptically or directly stimulated transient increases of calcium activity (Delta[Ca(2+)](i)) to transiently decrease and then to increase. In dissociated cells, lowering pi(o) by approximately 70 mOsm caused [Ca(2+)](i) to almost double on average from 83 to 155 nM. The increase of [Ca(2+)](i) was not significantly correlated with hypotonic cell swelling. Isoosmotic (mannitol- or sucrose-substituted) lowering of [NaCl](o), which did not cause cell swelling, also raised [Ca(2+)](i). Substituting NaCl with choline-Cl or Na-methyl-sulfate did not affect [Ca(2+)](i). In neurons bathed in calcium-free medium, lowering pi(o) caused a milder increase of [Ca(2+)](i), which was correlated with cell swelling, but in the absence of external Ca(2+), isotonic lowering of [NaCl](o) triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e., in both low pi(o) and low [NaCl](o)) causes a net influx of Ca(2+) from the extracellular medium whereas cell swelling, or the increase in membrane tension, is a signal for the release of Ca(2+) from intracellular stores.
authors.affiliation: Institute for Neurobiology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Borgdorff
authors.forename: G G
authors.initials: GG
authors.lastname: Somjen
authors.forename: W J
authors.initials: WJ
authors.lastname: Wadman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D048429:Cell Size; D002794:Choline / Q000494:pharmacology; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008353:Mannitol / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology*; D013395:Sucrose / Q000494:pharmacology
chemical_list: D005456:Fluorescent Dyes; D007038:Hypotonic Solutions; D008353:Mannitol; D012965:Sodium Chloride; D013395:Sucrose; D002794:Choline; D002118:Calcium