Enhanced fast synaptic transmission and a delayed depolarization induced by transient potassium current blockade in rat hippocampal slice as studied by optical recording

Michael E. Barish, Michinori Ichikawa, Takashi Tominaga, Gen Matsumoto, Toshio Iijima

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    Abstract

    In hippocampal neurons, a slowly inactivating aminopyridinesensitive transient potassium current, D-current, influences the time course of action potential repolarization and therefore activity-dependent Ca2+ entry. We used high-speed optical recording techniques to study the effects of selectively inhibiting D-current with 4-AP (40 μM) on transmission at the Schaffer collateral (CA3)-CA1 synapse in rat hippocampal slices stained with the voltage-sensitive dye RH-155. We observed that addition of 4-AP to the bathing solution resulted in (1) augmentation of a fast component of the optical signal corresponding to the postsynaptic EPSP and action potential, and (2) the appearance of a delayed depolarization of CA1 neurons and other adjacent cells. 4-AP appeared to alter the presynaptic action potential and the dynamics of synaptic transmission to both reduce the sensitivity of the postsynaptic EPSP and action potential to ω-toxin calcium channel blockers (ω-conotoxinGVIA and ω-agatoxin IVA) and the Ca2+ -dependent potassium channel blocker charybdotoxin, and to increase sensitivity to the dihydropyridine nifedipine, the NMDA receptor blocker aminophosphonopentanoic acid, and the intracellular Ca2+ release inhibitor thapsigargin. The delayed depolarization induced by 4-AP was inhibited in hyperosmotic extracellular solution, suggesting that enhanced transmitter release resulted in increased accumulation of K+ in the extracellular space. Because 4-AP is a convulsant at concentrations similar to those used here, we suggest that the 4-AP-targeted channel(s) carrying D-current may contribute to the hyperexcitability associated with epilepsy.

    Original languageEnglish
    Pages (from-to)5672-5687
    Number of pages16
    JournalJournal of Neuroscience
    Volume16
    Issue number18
    DOIs
    Publication statusPublished - 1996 Sep 15

    Keywords

    • 4-aminopyridine
    • A-current
    • D-current
    • RH-155
    • RH-482
    • epilepsy
    • hippocampus
    • microelectrode recording
    • optical recording
    • voltage-gated potassium current

    ASJC Scopus subject areas

    • Neuroscience(all)

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