Two mechanisms that raise free intracellular calcium in rat hippocampal neurons during hypoosmotic and low NaCl treatment.
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.
Borgdorff
A J
AJ
Institute for Neurobiology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands.
Somjen
G G
GG
Wadman
W J
WJ
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
D005456:Fluorescent Dyes; D007038:Hypotonic Solutions; D008353:Mannitol; D012965:Sodium Chloride; D013395:Sucrose; D002794:Choline; D002118:Calcium