Presynaptic ryanodine receptors are required for normal quantal size at the Caenorhabditis elegans neuromuscular junction

Qiang Liu, Bojun Chen, Maya Yankova, D. Kent Morest, Ed Maryon, Arthur R. Hand, Michael L. Nonet, Zhao Wen Wang

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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 Ca 2+ 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.

Original languageEnglish
Pages (from-to)6745-6754
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number29
DOIs
StatePublished - Jul 20 2005

Keywords

  • C. elegans
  • Calcium
  • Neuromuscular junction
  • Presynaptic
  • Quantal size
  • Ryanodine receptor

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