Distinct roles of Drosophila cacophony and Dmca1D Ca2+ channels in synaptic homeostasis: Genetic interactions with slowpoke Ca2+‐activated BK channels in presynaptic excitability and postsynaptic response

Ca²⁺ influx through voltage‐activated Ca²⁺ channels and its feedback regulation by Ca²⁺‐activated K⁺ (BK) channels is critical in Ca²⁺‐dependent cellular processes, including synaptic transmission, growth and homeostasis. Here we report differential roles of cacophony (Ca_V2) and Dmca1D (Ca_V1) Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ channels differentially contribute to functional and structural aspects of slo‐induced synaptic modifications. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 1–15, 2014