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4‐Chloro‐ m ‐cresol, an activator of ryanodine receptors, inhibits voltage‐gated K + channels at the rat calyx of Held
Author(s) -
Suzuki Daisuke,
Hori Tetsuya,
Saitoh Naoto,
Takahashi Tomoyuki
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05762.x
Subject(s) - ryanodine receptor , activator (genetics) , calyx , receptor , chemistry , neuroscience , biology , anatomy , biochemistry
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 Ca 2+ 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 m m . 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 ( I pK ) by 53% (at +20 mV) but had no effect on voltage‐gated presynaptic Ca 2+ currents ( I pCa ). In simultaneous pre‐ and postsynaptic recordings, 4‐CmC had no effect on the TIFC evoked by I pCa . Although immunocytochemical study of the calyceal terminals showed immunoreactivity to type 3 RyRs, ryanodine (0.02 m m ) 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 I pK .