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• W2021305863 abstract "Abstract Multiple Ca 2+ entry routes have been implicated in excitotoxic Ca 2+ loading in neurons and reverse‐operation of sodium–calcium exchangers (NCX) has been shown to contribute under conditions where intracellular Na + levels are enhanced. We have investigated effects of KB‐R7943, an inhibitor of reverse‐operation NCX activity, on Ca 2+ elevations in single CA1 neurons in acute hippocampal slices. KB‐R7943 had no significant effect on input resistance, action potential waveform, or action potential frequency adaptation, but reduced L‐type Ca 2+ entry in somata. Nimodipine was therefore included in subsequent experiments to prevent complication from effects of L‐type influx on evaluation of NCX activity. NMDA produced transient primary Ca 2+ increases, followed by propagating secondary Ca 2+ increases that initiated in apical dendrites. KB‐R7943 had no significant effect on primary or secondary Ca 2+ increases generated by NMDA. The Na + /K + ATPase inhibitor ouabain (30 μM) produced degenerative Ca 2+ overload that was initiated in basal dendrites. KB‐R7943 significantly reduced initial Ca 2+ increases and delayed the propagation of degenerative Ca 2+ loads triggered by ouabain, raising the possibility that excessive intracellular Na + loading can trigger reverse‐operation NCX activity. A combination of NMDA and ouabain produced more rapid Ca 2+ overload, that was contributed to by NCX activity. These results suggest that degenerative Ca 2+ signaling can be triggered by NMDA in dendrites, before intracellular Na + levels become sufficient to reverse NCX activity. However, since Na + /K + ATPase inhibition does appear to produce significant reverse‐operation NCX activity, this additional Ca 2+ influx pathway may operate in ATP‐deprived CA1 neurons and play a role in ischemic neurodegeneration. © 2007 Wiley‐Liss, Inc." @default.
• W2021305863 created "2016-06-24" @default.
• W2021305863 creator A5045364135 @default.
• W2021305863 creator A5057819973 @default.
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• W2021305863 date "2007-06-27" @default.
• W2021305863 modified "2023-10-11" @default.
• W2021305863 title "Contribution of Na+/Ca2+ exchange to excessive Ca2+ loading in dendrites and somata of CA1 neurons in acute slice" @default.
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• W2021305863 doi "https://doi.org/10.1002/hipo.20336" @default.
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