Effects of prolonged elevation of potassium on hippocampus of anesthetized rats.
We tested the after-effects of prolonged depolarization on neurons in situ in the mammalian brain and examined the site of blockade responsible for failure of synaptic transmission. The CA1 region of the hippocampus of anesthetized rats was exposed to solutions containing elevated concentration of K+ (100-125 mmol/l), administered either by microdialysis in intact brain or by irrigation of the exposed surface of the hippocampus. Recovery was observed for 5-6 1/2 h. When K+ was administered by microdialysis, evoked potentials were recorded from points near (up to 0.2 mm) and far (0.7-1.0 mm) from the dialysis probe. High K+ dialysis induced recurrent waves of spreading depression and, in about half of the preparations, a prolonged unstable depressed state. In the intervals between SD waves orthodromic but not antidromic population spikes remained severely depressed at the 'far' recording site. Following high K+ dialysis orthodromic population spikes recovered in a triphasic cycle: partial recovery with hyper-transmission was followed by secondary depression and finally by slow partial or complete recovery. Final recovery was less complete in cases that have experienced prolonged spreading depression. Current source density analysis revealed that during secondary depression transmission was blocked due to failure of dendritic action potentials. When the exposed hippocampus was irrigated with high K+ solution ortho- and antidromic evoked potentials recovered completely following high K+ exposure of less than 30 min, incompletely after 45 min and failed entirely after 60 min. We conclude that prolonged steady depolarization of hippocampal CA1 pyramidal neurons causes lasting loss of function. Dendritic function is especially prone to depolarization-induced injury. CA1 neurons are less vulnerable in situ than they are in vitro.
Herreras
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Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
Somjen
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D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects; D003956:Dialysis; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014520:Urethane
D014520:Urethane; D011188:Potassium