The extent and mechanism of the loss of function caused by strongly hypotonic solutions in rat hippocampal slices.
To investigate whether prolonged severe swelling would cause irreversible injury to neurons, we exposed hippocampal tissue slices to hypotonic solutions (142 mosmol/kg) and followed the recovery of evoked responses for 5 h. Orthodromically evoked responses increased during hypotonia, except during recurrent waves of spreading depression (SD). After restoring normal osmotic pressure (pi o), evoked potentials became profoundly depressed. Following 30 min exposure, nearly maximal orthodromic responses recovered completely but responses to submaximal stimuli remained depressed, indicating elevated threshold. Following 60 min exposure, orthodromic transmission remained depressed. In slices from young animals, antidromic population spikes recovered completely, but in slices from older rats they remained partly depressed. Withdrawing calcium and raising magnesium concentration before and during hypotonic exposure resulted in modest but significant improvement of the recovery of synaptically transmitted responses, but made no difference for antidromic responses. With [Ca2+]o reduced and [Mg2+]o elevated, electrographic seizures replaced the episodes of SD during low pi o treatment. We conclude that even 60 min of severe hypotonic swelling did not kill CA1 pyramidal cells in tissue from young rats, but in its aftermath synaptic transmission was disrupted. Uptake of calcium may have played a minor role in the impairment of synaptic transmission. We propose hypothetically that post-hypotonic shrinkage of dendrites disrupted the integrity of excitatory synapses.
Huang
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Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Aitken
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Somjen
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D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000502:physiology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
D007038:Hypotonic Solutions; D002118:Calcium