title: Presynaptic ryanodine receptors are required for normal quantal size at the Caenorhabditis elegans neuromuscular junction.
abstract: Analyses of the effect of ryanodine in vertebrate brain slices have led to the conclusion that presynaptic ryanodine receptors (RYRs) may have several functions in synaptic release, including causing large-amplitude miniature postsynaptic currents (mPSCs) by promoting concerted multivesicular release. However, the role of RYRs in synaptic release is controversial. To better understand the role of RYRs in synaptic release, we analyzed the effect of RYR mutation on mPSCs and evoked postsynaptic currents (ePSCs) at the Caenorhabditis elegans neuromuscular junction (NMJ). Amplitudes of mPSCs varied greatly at the C. elegans NMJ. Loss-of-function mutations of the RYR gene unc-68 (uncoordinated 68) essentially abolished large-amplitude mPSCs. The amplitude of ePSCs was also greatly suppressed. These defects were completely rescued by expressing wild-type UNC-68 specifically in neurons but not in muscle cells, suggesting that RYRs acted presynaptically. A combination of removing extracellular Ca2+ and UNC-68 function eliminated mPSCs, suggesting that influx and RYR-mediated release are likely the exclusive sources of Ca2+ for synaptic release. Large-amplitude mPSCs did not appear to be caused by multivesicular release, as has been suggested to occur at vertebrate central synapses, because the rise time of mPSCs was constant regardless of the amplitude but distinctive from that of ePSCs, and because large-amplitude mPSCs persisted under conditions that inhibit synchronized synaptic release, including elimination of extracellular Ca2+, and mutations of syntaxin and SNAP25 (soluble N-ethylmaleimide-sensitive factor attachment protein 25). These observations suggest that RYRs are essential to normal quantal size and are potential regulators of quantal size.
authors: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA.
authors: Qiang
authors: Q
authors: Liu
authors: Bojun
authors: B
authors: Chen
authors: Maya
authors: M
authors: Yankova
authors: D Kent
authors: DK
authors: Morest
authors: Ed
authors: E
authors: Maryon
authors: Arthur R
authors: AR
authors: Hand
authors: Michael L
authors: ML
authors: Nonet
authors: Zhao-Wen
authors: ZW
authors: Wang
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D008854:Microscopy, Electron; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure; D017661:Receptors, Presynaptic / Q000502:physiology* / Q000648:ultrastructure; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D017661:Receptors, Presynaptic; D019837:Ryanodine Receptor Calcium Release Channel; C438601:Unc-68 protein, C elegans; D012433:Ryanodine; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D002118:Calcium