title: Type-3 ryanodine receptor involved in Ca2+-induced Ca2+ release and transmitter exocytosis at frog motor nerve terminals.
abstract: Ca(2+)-induced Ca2+ release (CICR) occurs in frog motor nerve terminals after ryanodine receptors (RyRs) are primed for activation by conditioning large Ca2+ entry. We studied which type of RyR exists, whether CICR occurs without conditioning Ca2+ entry and how RyRs are primed. Immunohistochemistry revealed the existence of RyR3 in motor nerve terminals and axons and both RyR1 and RyR3 in muscle fibers. A blocker of RyR, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) slightly decreased rises in intracellular Ca2+ ([Ca2+]i) induced by a short tetanus (50 Hz, 1-2s), but not after treatment with ryanodine. Repetitive tetani (50 Hz for 15s every 20s) produced repetitive rises in [Ca2+]i, whose amplitude overall waxed and waned. TMB-8 blocked the waxing and waning components. Ryanodine suppressed a slow increase in end-plate potentials (EPPs) induced by stimuli (33.3 Hz, 15s) in a low Ca2+, high Mg2+ solution. KN-62, a blocker of Ca(2+)/calmoduline-activated protein kinase II (CaMKII), slightly reduced short tetanus-induced rises in [Ca2+]i, but markedly the slow waxing and waning rises produced by repetitive tetani in both normal and low Ca2+, high Mg2+ solutions. Likewise, KN-62, but not KN-04, an inactive analog, suppressed slow increases in EPP amplitude and miniature EPP frequency during long tetanus. Thus, CICR normally occurs weakly via RyR3 activation by single impulse-induced Ca2+ entry in frog motor nerve terminals and greatly after the priming of RyR via CaMKII activation by conditioning Ca2+ entry, thus, facilitating transmitter exocytosis and its plasticity.
authors.affiliation: Department of Physiology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kubota
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Narita
authors.forename: Takashi
authors.initials: T
authors.lastname: Murayama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Satoko
authors.initials: S
authors.lastname: Soga
authors.forename: Jiro
authors.initials: J
authors.lastname: Usukura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuba
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D011898:Ranidae; D019837:Ryanodine Receptor Calcium Release Channel / Q000145:classification* / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium