Anoxia in CA1 Pyramidal Cells: Ionic and Metabolic Factors Contributing to Recovery of Ion Transport and Synaptic Transmission

Abstract

Ionic and electrophysiological characteristics of CA1 pyramidal cells were studied in hippocampal slices during and following anoxia to further understand the sensitivity of these neurons to anoxia. The response of these neurons to anoxia differs from other hippocampal neurons, for example dentate granule cells, in that early after the onset of anoxia synaptic transmission fails apparently due to neuronal hyperpolarization. In contrast, other investigators have reported that dentate granule cells depolarize steadily during anoxia. It remains possible that the ionic conductance properties of CA1 pyramidal cells which cause the hyperpolarizing response to anoxia also render these cells susceptible to long term anoxic damage. We also investigated ion transport dysfunction in hippocampal subfield CA1 following brief anoxia. Reaccumulation of potassium ion, released into the extracellular space during anoxia, was impaired if the duration of anoxic depolarization was sufficiently long. Potassium transport dysfunction was exaccerbated by high calcium treatment and was prevented if extracellular calcium was lowered. Recovery of synaptic transmission following anoxia always was correlated with potassium transport dysfunction. That is, if reaccumulation of potassium ion was impaired, so also was recovery of synaptic transmission. These studies suggest that influx of calcium ion into neurons during the period of anoxic depolarization causes damage to cell metabolism, likely mithochondrial damage, which impairs active ion transport. If this impairment includes the active transport or active sequestration of calcium ion, then long-term inhibition of synaptic transmission will ensue.