Pharmacological dissection of calcium channel subtype-related components of strontium inflow in large mossy fiber boutons of mouse hippocampus

Takashi Tokunaga, Kenichi Miyazaki, Makoto Koseki, Jalal Izadi Mobarakeh, Toru Ishizuka, Hiromu Yawo

    Research output: Contribution to journalReview articlepeer-review

    25 Citations (Scopus)

    Abstract

    Several subtypes of voltage-dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q-, N-, and R- but not L-type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L-type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus-evoked Sr2+ increment (Δ[Sr2+]pre) was evaluated fluorometrically. Δ[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype-selective antagonists. The P/Q-type selective ω-agatoxin IVA (AgTxIVA) blocked Δ[Sr2+]pre with an IC50 of 28 nM and by 30-35% at its maximum effective concentration of 0.5 μM. The N-type selective ω-conotoxin GVIA (CgTxGVIA) blocked Δ[Sr2+]pre with an IC50 of 15 nM and by 20-25% at its maximum effective concentration of 1 μM. The R-type selective SNX-482 blocked Δ[Sr2+]pre with an IC50 of 79 nM and by 20-25% at its maximum effective concentration of 1 μM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70-80% of Δ[Sr2+]pre was blocked by the simultaneous exposure to these toxins. Δ[Sr2+]pre component that is resistant to AgTxIVA, CgTxGVIA, and SNX-482 was significantly potentiated by an L-type agonist, (S)-(-)-Bay K8644, and attenuated by an L-type antagonist, nimodipine, suggesting that L-type VDCCs are present in large MF terminals. The L-type agonist, (±)-Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow-dependent fluorescence increments. L-type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials.

    Original languageEnglish
    Pages (from-to)570-585
    Number of pages16
    JournalHippocampus
    Volume14
    Issue number5
    DOIs
    Publication statusPublished - 2004

    Keywords

    • Agatoxin
    • Bay K8644
    • Conotoxin
    • Presynaptic terminal
    • SNX-482

    ASJC Scopus subject areas

    • Cognitive Neuroscience

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