Distinct roles of Drosophila cacophony and Dmca1D Ca(2+) channels in synaptic homeostasis: genetic interactions with slowpoke Ca(2+) -activated BK channels in presynaptic excitability and postsynaptic response

Dev Neurobiol. 2014 Jan;74(1):1-15. doi: 10.1002/dneu.22120. Epub 2013 Oct 7.

Abstract

Ca(2+) influx through voltage-activated Ca(2+) channels and its feedback regulation by Ca(2+) -activated K(+) (BK) channels is critical in Ca(2+) -dependent cellular processes, including synaptic transmission, growth and homeostasis. Here we report differential roles of cacophony (CaV 2) and Dmca1D (CaV 1) Ca(2+) channels in synaptic transmission and in synaptic homeostatic regulations induced by slowpoke (slo) BK channel mutations. At Drosophila larval neuromuscular junctions (NMJs), a well-established homeostatic mechanism of transmitter release enhancement is triggered by experimentally suppressing postsynaptic receptor response. In contrast, a distinct homeostatic adjustment is induced by slo mutations. To compensate for the loss of BK channel control presynaptic Sh K(+) current is upregulated to suppress transmitter release, coupled with a reduction in quantal size. We demonstrate contrasting effects of cac and Dmca1D channels in decreasing transmitter release and muscle excitability, respectively, consistent with their predominant pre- vs. postsynaptic localization. Antibody staining indicated reduced postsynaptic GluRII receptor subunit density and altered ratio of GluRII A and B subunits in slo NMJs, leading to quantal size reduction. Such slo-triggered modifications were suppressed in cac;;slo larvae, correlated with a quantal size reversion to normal in double mutants, indicating a role of cac Ca(2+) channels in slo-triggered homeostatic processes. In Dmca1D;slo double mutants, the quantal size and quantal content were not drastically different from those of slo, although Dmca1D suppressed the slo-induced satellite bouton overgrowth. Taken together, cac and Dmca1D Ca(2+) channels differentially contribute to functional and structural aspects of slo-induced synaptic modifications.

Keywords: Dmca1D (CaV1); EJPs; cacophony (CaV2); larval neuromuscular junction (NMJ); mEJPs; slowpoke (BK); spontaneous vesicle release; synaptic homeostasis; synaptic transmission.

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / physiology*
  • Charybdotoxin / pharmacology
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / physiology*
  • Electric Stimulation
  • Electrophysiological Phenomena / physiology
  • Excitatory Postsynaptic Potentials / physiology
  • Homeostasis / genetics*
  • Homeostasis / physiology*
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Large-Conductance Calcium-Activated Potassium Channels / physiology*
  • Muscles / physiology
  • Mutation / genetics
  • Mutation / physiology
  • Neuromuscular Junction / physiology
  • Neurotoxins / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / physiology
  • Presynaptic Terminals / physiology
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / physiology
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Ca-alpha1D protein, Drosophila
  • Calcium Channels
  • Drosophila Proteins
  • Large-Conductance Calcium-Activated Potassium Channels
  • Neurotoxins
  • Potassium Channels
  • Receptors, Glutamate
  • cac protein, Drosophila
  • slo protein, Drosophila
  • Charybdotoxin
  • Tetrodotoxin