title: Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K+ in hippocampus of anesthetized rats.
abstract: The potential shifts (delta Vo) associated with spreading depression (SD) were analysed with the help of multiple extracellular recording and ion-selective microelectrodes in the CA1 region of the dorsal hippocampus of anesthetized rats. Recurrent waves of SD were induced by perfusing high K+ solution through microdialysis probes. SD-related delta Vo had a composite wave shape, consisting of an early, rapidly shifting part (phase I) followed by a slower shift to a second negative maximum (phase II). delta Vo shifts in stratum radiatum usually started earlier, always lasted longer and had larger amplitude than those recorded in stratum pyramidale. The delta Vo responses in stratum radiatum had an inverted saddle shape created by a transient relatively positive "hump" interposed between phases I and II. During this "hump", the potentials in the two layers transiently approached one another. During continuous high K+ dialysis, successive delta Vo waves episodes evolved according to a consistent pattern: while phase I remained unchanged, phase II increased in amplitude and duration with each episode. Eventually, a depressed state developed which lasted for many minutes, termed here prolonged unstable spreading depression. During phase I, delta Vo and extracellular K ([K+]o) changes were correlated. During phase II, [K+]o decreased even as delta Vo continued to increase. During SD, [Ca2+]o decreased to < 0.01 mM. During phases I and II, both [Ca2+]o and [Na+]o remained low. The recoveries of [Ca2+]o and [Na+]o had an initial fast and a later much slower phase and took several minutes longer than the recoveries of [K+]o and delta Vo. Depth profiles of delta Vo and delta [K+]o revealed strikingly steep gradients early and late during a wave; but voltage and ion gradients were not precisely correlated either in time or in space. We conclude that delta Vo of phases I and II are generated by different processes. Membrane ion currents cannot fully explain the delta Vo responses. The possible contributions by ion diffusion and by active ion transport are discussed. The extremely low level to which [Ca2+]o sinks during SD, and its two-phase recovery, indicate intracellular sequestration or binding of substantial amounts of Ca2+ ions. The residual deficit of [Ca2+]o following recovery of SP shifts may account for the persistent depression of synaptic transmission after repolarization of neurons.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.
authors.forename: O
authors.initials: O
authors.lastname: Herreras
authors.forename: G G
authors.initials: GG
authors.lastname: Somjen
mesh_terms: D000758:Anesthesia; D000818:Animals; D002118:Calcium / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects; D003956:Dialysis; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008839:Microelectrodes; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism
chemical_list: D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D012964:Sodium; D011188:Potassium; D002118:Calcium