Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release
Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release
复制标题
DOI：
10.1007/s004240100691
复制
发表时间：
2001-11-01
影响因子：
4.5
通讯作者：
Baux, G
中科院分区：
文献类型：
--
作者：
Chameau, P;Van de Vrede, Y;Baux, G
将肌醇三磷酸(IP3)或烟酰胺腺嘌呤二核苷酸磷酸(NAADP)注射到加州海兔颊神经节胆碱能突触的突触前神经元内，可增加突触前动作电位诱发的抑制性突触后电流的幅度。这表明，各种钙库中的钙离子释放对乙酰胆碱(ACh)的释放具有调节性作用。用ryanodine特异性阻断钙诱导的钙释放(CICR)机制，或用肝素阻断IP3诱导的钙释放，可取消IP3的作用，但不能阻断NAADP的作用，提示细胞内存在独立于含有ryanodine受体(RyR)或IP3受体的钙池。为了加强电生理观察，使用荧光染料Rhod-2测量了细胞内[Ca~(2+)]的变化。突触前神经元注射环状ADP核糖(RyR激活剂)、IP3或NAADP可引起突触前神经元细胞内游离钙浓度一过性升高。应用各自的选择性拮抗剂可阻止RyR和IP3诱导的增加，但不能阻止NAADP诱导的增加。我们的结果表明，依赖于RyR、依赖于IP3和依赖于NAADP的钙库存在于相同的突触前终末，但它们参与了触发递质释放的突触前钙离子浓度的调节。
Injections of inositol trisphosphate (IP3) or nicotinamide adenine dinucleotide phosphate (NAADP) into the presynaptic neurone of an identified cholinergic synapse in the buccal ganglion of Aplysia californica increased the amplitude of the inhibitory postsynaptic current evoked by a presynaptic action potential. This suggests that Ca2+ release from various Ca2+ stores can modulate acetylcholine (ACh) release. Specific blockade of the calcium-induced calcium release (CICR) mechanism with ryanodine, or of IP3-induced calcium release with heparin, abolished the effects Of IP3, but not the effects of NAADP, suggesting the presence of an intracellular Ca2+ pool independent of those containing ryanodine receptors (RyR) or IP3 receptors. To reinforce electrophysiological observations, intracellular [Ca2+], changes were measured using the fluorescent dye rhod-2. Injections of cyclic ADP-ribose (an activator of RyR), IP3 or NAADP into the presynaptic neurone induced transient increases in the free intracellular Ca2+ concentration. RyR- and IP3-induced increases were prevented by application of respective selective antagonists but not NAADP-induced increases. Our results show that RyR-dependent, IP3-dependent, and NAADP-dependent Ca2+ stores are present in the same presynaptic terminal but are differently involved in the regulation of the presynaptic Ca2+ concentration that triggers transmitter release.