4-Chloro-m-cresol, an activator of ryanodine receptors, inhibits voltage-gated K+ channels at the rat calyx of Held

Authors

  • Daisuke Suzuki,

    1. Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
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  • Tetsuya Hori,

    1. Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    2. Department of Neurophysiology, Doshisha University Faculty of Life and Medical Sciences, Kyoto 619-0225, Japan
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  • Naoto Saitoh,

    1. Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    2. Department of Neurophysiology, Doshisha University Faculty of Life and Medical Sciences, Kyoto 619-0225, Japan
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  • Tomoyuki Takahashi

    1. Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    2. Department of Neurophysiology, Doshisha University Faculty of Life and Medical Sciences, Kyoto 619-0225, Japan
    3. Cellular & Molecular Synaptic Function Unit, Initial Research Project, Okinawa Institute of Science and Technology Promotion Corporation, Uruma, Okinawa, Japan
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Dr Tomoyuki Takahashi, 2Department of Neurophysiology, as above.
E-mail: ttakahas@mail.doshisha.ac.jp

Abstract

4-Chloro-m-cresol (4-CmC) is thought to be a specific activator of ryanodine receptors (RyRs). Using this compound, we examined whether the RyR-mediated Ca2+ release is involved in transmitter release at the rat calyx of Held synapse in brainstem slices. Bath application of 4-CmC caused a dramatic increase in the amplitude of excitatory postsynaptic currents (TIFCs) with the half-maximal effective concentration of 0.12 mm. By making direct patch-clamp whole-cell recordings from presynaptic terminals, we investigated the mechanism by which 4-CmC facilitates transmitter release. 4-CmC markedly prolonged the duration of action potentials, with little effect on their rise time kinetics. In voltage-clamp recordings, 4-CmC inhibited voltage-gated presynaptic K+ currents (IpK) by 53% (at +20 mV) but had no effect on voltage-gated presynaptic Ca2+ currents (IpCa). In simultaneous pre- and postsynaptic recordings, 4-CmC had no effect on the TIFC evoked by IpCa. Although immunocytochemical study of the calyceal terminals showed immunoreactivity to type 3 RyRs, ryanodine (0.02 mm) had no effect on the 4-CmC-induced TIFC potentiation. We conclude that the facilitatory effect of 4-CmC on nerve-evoked transmitter release is mediated by its inhibitory effect on IpK.

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