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This Article Full Text Full Text (PDF) All Versions of this Article: 551/2/403    most recent jphysiol.2003.041723v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ichinose, T. Articles by Yu, S. P. Search for Related Content PubMed PubMed Citation Articles by Ichinose, T. Articles by Yu, S. P.

Ca²⁺-independent, but voltage- and activity-dependent regulation of the NMDA receptor outward K⁺ current in mouse cortical neurons

Tomomi Ichinose*, Shun Yu†, Xue Qing Wang*† and Shan Ping Yu*†

To test the novel hypothesis that the K⁺ efflux mediated by NMDA receptors might be regulated differently than the influx of Ca²⁺ and Na⁺ through the same receptor channels, NMDA receptor whole-cell currents carried concurrently or individually by Ca²⁺, Na⁺ and K⁺ were analysed in cultured mouse cortical neurons. In contrast to the NMDA inward current carried by Ca²⁺ and Na⁺, the NMDA receptor outward K⁺ current or NMDA-K current, recorded either in the presence or absence of extracellular Ca²⁺ and Na⁺, and at different or the same membrane potentials, showed much less sensitivity to alterations in intracellular Ca²⁺ concentration and underwent little rundown. In line with a selective regulation of the NMDA receptor K⁺ permeability, the ratio of the NMDA inward/outward currents decreased, and the reversal potential of composite NMDA currents recorded in physiological solutions shifted by -8.5 mV after repeated activation of NMDA receptors. Moreover, a depolarizing pre-pulse of a few seconds or a burst of brief depolarizing pulses selectively augmented the subsequent NMDA-K current, but not the NMDA inward current. On the other hand, a hyperpolarizing pre-pulse showed the opposite effect of reducing the NMDA-K current. The voltage- and activity-dependent regulation of the NMDA-K current did not require the existence of extracellular Ca²⁺ or Ca²⁺ influx; it was, however, affected by the duration of the pre-pulse and was subject to a time-dependent decay. The burst of excitatory activity revealed a lasting upregulation of the NMDA-K current even 5 s after termination of the pre-pulses. Our data reveal a selective regulation of the NMDA receptor K⁺ permeability and represent a novel model of voltage- and excitatory activity-dependent plasticity at the receptor level.

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