Two Mechanisms That Raise Free Intracellular Calcium In Rat Hippocampal Neurons During Hypo-Osmotic And Low Nacl Treatment. Aren J. Borgdorff1, George G. Somjen2 and Wytse J. Wadman1. 1Institute for Neurobiology, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, the Netherlands and 2Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
APStracts 6:0494N, 1999.
Previous studies have shown that exposing hippocampal slices to low osmolarity (?o) or to low extracellular NaCl concentration ([NaCl]o) enhances synaptic transmission and also causes interstitial calcium ([Ca2+]o) to decrease (Chebabo et al. 1995a; Chebabo et al. 1995b; Huang et al. 1997). Reduction of [Ca2+]o suggests cellular uptake and could explain the potentiation of synaptic transmission. We now measured intracellular calcium activity ([Ca2+]i) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices lowering of ?o by about 70 mOsm caused "resting" [Ca2+]i as well as synaptically or directly stimulated transient increases of calcium activity (([Ca2+]i) to transiently decrease and then to increase. In dissociated cells, lowering ?o by about 70 mOsm caused [Ca2+]i to almost double on average from 83 nM to 155 nM. The increase of [Ca2+]i was not significantly correlated with hypotonic cell swelling. Iso-osmotic (mannitol- or sucrose-substituted) lowering of [NaCl]o, which did not cause cell swelling, also raised [Ca2+]i. Substituting NaCl by Choline-Cl or by Na-methyl-sulfate did not affect [Ca2+]i. In neurons bathed in calcium-free medium lowering of ?o caused a milder increase of [Ca2+]i which was correlated with cell swelling, but in the absence of external Ca2+ isotonic lowering of [NaCl]o triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e. in both low ?o and low [NaCl]o) causes a net influx of Ca2+ from the extracellular medium, while cell swelling, or the increase in membrane tension, is a signal for the release of Ca2+ from intracellular stores.
Received 10 June 1999; accepted in final form 1 October 1999.
APS Manuscript Number J485-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999