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The Journal of Neuroscience, June 15, 2001, 21(12):4173-4182
Extracellular Calcium Modulates Persistent Sodium Current-Dependent Burst-Firing in Hippocampal Pyramidal Neurons
Hailing Su, Gil Alroy, Eilon D. Kirson, and Yoel Yaari Department of Physiology, Institute of Medical Sciences, The Hebrew University-Hadassah Faculty of Medicine, Jerusalem 91120, Israel
The generation of high-frequency spike bursts ("complex spikes"), either spontaneously or in response to depolarizing stimuli applied to the soma, is a notable feature in intracellular recordings from hippocampal CA1 pyramidal cells (PCs) in vivo. There is compelling evidence that the bursts are intrinsically generated by summation of large spike afterdepolarizations (ADPs). Using intracellular recordings in adult rat hippocampal slices, we show that intrinsic burst-firing in CA1 PCs is strongly dependent on the extracellular concentration of Ca2+ ([Ca2+]o). Thus, lowering [Ca2+]o (by equimolar substitution with Mn2+ or Mg2+) induced intrinsic bursting in nonbursters, whereas raising [Ca2+]o suppressed intrinsic bursting in native bursters. The induction of intrinsic bursting by low [Ca2+]o was associated with enlargement of the spike ADP. Low [Ca2+]o-induced intrinsic bursts and their underlying ADPs were suppressed by drugs that reduce the persistent Na+ current (INaP), indicating that this current mediates the slow burst depolarization. Blocking Ca2+-activated K+ currents with extracellular Ni2+ or intracellular chelation of Ca2+ did not induce intrinsic bursting. This and other evidence suggest that lowering [Ca2+]o may induce intrinsic bursting by augmenting INaP. Because repetitive neuronal activity in the hippocampus is associated with marked decreases in [Ca2+]o, the regulation of intrinsic bursting by extracellular Ca2+ may provide a mechanism for preferential recruitment of this firing mode during certain forms of hippocampal activation.
Key words: intrinsic bursting; calcium; persistent sodium current; pyramidal cell; hippocampus; phenytoin; gap junction; PKC; rat
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124173-10$05.00/0
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