Presynaptic Ryanodine Receptors Are Required for Normal Quantal Size at theCaenorhabditis elegansNeuromuscular Junction

Authors:
  • BCBojun Chen
    Bojun Chen
  • MYMaya Yankova
    Maya Yankova
  • DMD. Kent Morest
    D. Kent Morest
  • EMEd Maryon
    Ed Maryon
  • AHArthur R. Hand
    Arthur R. Hand
  • MNMichael L. Nonet
    Michael L. Nonet
  • ZWZhao-Wen Wang
    Zhao-Wen Wang
Open Access
Publisher website
Google Scholar
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 theCaenorhabditis elegansneuromuscular junction (NMJ). Amplitudes of mPSCs varied greatly at theC. elegansNMJ. Loss-of-function mutations of the RYR geneunc-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 (solubleN-ethylmaleimide-sensitive factor attachment protein 25). These observations suggest that RYRs are essential to normal quantal size and are potential regulators of quantal size.

This publication has 59 references indexed in Scilit: