Hypotonic exposure enhances synaptic transmission and triggers spreading depression in rat hippocampal tissue slices.
Low extracellular osmotic pressure (pi o) is known to enhance CNS responsiveness and the chance of seizures, but the mechanism of the hyperexcitability is not clear. We recorded evoked potentials in st. radiatum and st. pyramidale of CA1. Tissue electrical resistance (Ro) was determined from the voltage drop (VRo) evoked by constant current pulses. Lowering of pi o by reducing [NaCl] caused a concentration-dependent increase of amplitude and duration of extracellular excitatory postsynaptic potentials (fEPSPs). fEPSPs increased much more than did VRo, but antidromic population spikes increased in proportion to VRo. fEPSP increased also in isosmotic low NaCl (fructose or mannitol substituted) solutions, but not as much as in low pi o. In moderately hypotonic solutions orthodromic population spikes increased as expected from the augmented fEPSP, but in strong hypotonia input-output curves shifted to the left and single stimuli evoked multiple population spikes, indicating lowering of threshold of postsynaptic neurons. Blocking N-methyl-D-aspartate (NMDA) receptors did not diminish the enhancement of fEPSP amplitude. Spreading depression (SD) erupted in most slices in very low pi o, but not in isoosmotic low [NaCl] solutions. We conclude that the hypotonic enhancement of EPSPs depends, in part, on the lowering of [Na+]o and/or of [Cl-]o, and it may be augmented by dendritic swelling favoring electrotonic spread of EPSPs from dendrites to somata, and buildup of transmitter concentration due to swelling of perisynaptic glia. SD can be initiated by cell swelling, but the depolarization associated with SD is probably not caused by the opening of stretch-gated ion channels.
Chebabo
S R
SR
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Hester
M A
MA
Aitken
P G
PG
Somjen
G G
GG
D000818:Animals; D048429:Cell Size / Q000502:physiology; D013181:Cortical Spreading Depression / Q000502:physiology*; D017097:Electric Impedance; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D006624:Hippocampus / Q000502:physiology* / Q000648:ultrastructure; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008839:Microelectrodes; D009994:Osmolar Concentration; D017966:Pyramidal Cells / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*
D007038:Hypotonic Solutions; D012965:Sodium Chloride