Lasting neuron depression induced by high potassium and its prevention by low calcium and NMDA receptor blockade.
Spreading depression-like neuron depolarization was induced in CA1 of hippocampal tissue slices by irrigation with artificial cerebrospinal fluid containing 133.5 mM K+ for 8-40 min. Evoked responses disappeared during irrigation with high-K+ solution. Following 8-20 min irrigation orthodromic responses showed a triphasic recovery cycle: early partial return with evidence of neuron hyperexcitability, then secondary depression and finally slow partial recovery. After 30 min or more of high-K+ exposure, ortho- and antidromic responses remained severely depressed for at least 5.5 to 6.5 h. When, however, the tissue was deprived of calcium, or N-methyl-D-aspartate (NMDA) receptors were blocked by 10 microM 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), then evoked responses recovered partially after a 30- or 40-min high-K+ exposure. Post-exposure hyperexcitability was not prevented by CPP. We conclude that prolonged depolarization by elevated K+ causes irreversible neuron damage, which is triggered or accelerated by influx of calcium ions into neurons, mediated in part by NMDA receptor activation.
Jing
J
J
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
Aitken
P G
PG
Somjen
G G
GG
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D011188:Potassium; D002118:Calcium