Type-3 ryanodine receptor involved in Ca²⁺-induced Ca²⁺ release and transmitter exocytosis at frog motor nerve terminals

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• 作者：Masakazu Kubota ; Kazuhiko Narita ; Takashi Murayama ; Shinichi Suzuki ; Satoko Soga ; Jiro Usukura ; Yasuo Ogawa ; Kenji Kuba
• 关键词：Ca²⁺-induced Ca²⁺ release ; Type-3 ryanodine receptor ; Presynaptic terminal ; Transmitter exocytosis ; Plasticity ; Frog neuromuscular junction
• 刊名：Cell Calcium
• 出版年：2005
• 出版时间：December 2005
• 年：2005
• 卷：38
• 期：6
• 页码：557-567
• 全文大小：784 K

文摘

Ca²⁺-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, 1–2 s), but not after treatment with ryanodine. Repetitive tetani (50 Hz for 15 s every 20 s) 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, 15 s) in a low Ca²⁺, high Mg²⁺ solution. KN-62, a blocker of Ca²⁺/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.