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

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.

Lee J#1,2, Ueda A#3, Wu CF1,3.

Author information

1
Interdisciplinary Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA.
2
Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan-Si, Kyoungsangnam-Do, 626-870, Korea.
3
Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
#
Contributed equally

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

PMID:
23959639
PMCID:
PMC3859705
DOI:
10.1002/dneu.22120
[Indexed for MEDLINE]
Free PMC Article

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