title: 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.
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.
authors: Interdisciplinary Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA.|Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan-Si, Kyoungsangnam-Do, 626-870, Korea.
authors: Jihye
authors: J
authors: Lee
authors: Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors: Atsushi
authors: A
authors: Ueda
authors: Interdisciplinary Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA.|Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
authors: Chun-Fang
authors: CF
authors: Wu
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000502:physiology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: C112195:Ca-alpha1D protein, Drosophila; D015220:Calcium Channels; D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D015221:Potassium Channels; D017470:Receptors, Glutamate; C472405:cac protein, Drosophila; C494844:slo protein, Drosophila; D018999:Charybdotoxin; D013779:Tetrodotoxin
keywords: Dmca1D (CaV1); EJPs; cacophony (CaV2); larval neuromuscular junction (NMJ); mEJPs; slowpoke (BK); spontaneous vesicle release; synaptic homeostasis; synaptic transmission
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