Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release.
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+]i 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.
Chameau
P
P
Laboratoire de Neurobiologie Cellulaire et Moléculaire, C.N.R.S., 91198 Gif-sur-Yvette cedex, France.
Van de Vrede
Y
Y
Fossier
P
P
Baux
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D002610:Cheek / Q000294:innervation; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D002118:Calcium