title: Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain.
abstract: Voltage-gated calcium channels containing alpha1 subunits encoded by Ca(v)2 family genes are critical in regulating release of neurotransmitter at chemical synapses. In Drosophila, cac is the only Ca(v)2-type gene. Cacophony (CAC) channels are localized in motor neuron terminals where they have been shown to mediate evoked, but not AP-independent, release of glutamate at the larval neuromuscular junction (NMJ). Cultured embryonic neurons also express CAC channels, but there is no information about the properties of CAC-mediated currents in adult brain nor how these channels regulate transmission in central neural circuits where fast excitatory synaptic transmission is predominantly cholinergic. Here we report that wild-type neurons cultured from late stage pupal brains and antennal lobe projection neurons (PNs) examined in adult brains, express calcium currents with two components: a slow-inactivating current sensitive to the spider toxin Plectreurys toxin II (PLTXII) and a fast-inactivating PLTXII-resistant component. CAC channels are the major contributors to the slow-inactivating PLTXII-sensitive current based on selective reduction of this component in hypomorphic cac mutants (NT27 and TS3). Another characteristic of cac mutant neurons both in culture and in whole brain recordings is a reduced cholinergic miniature excitatory postsynaptic current frequency that is mimicked in wild-type neurons by acute application of PLTXII. These data demonstrate that cac encoded Ca(v)2-type calcium channels regulate action potential (AP)-independent release of neurotransmitter at excitatory cholinergic synapses in the adult brain, a function not predicted from studies at the larval NMJ.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Gu
authors.forename: Shaojuan Amy
authors.initials: SA
authors.lastname: Jiang
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Campusano
authors.forename: Jorge
authors.initials: J
authors.lastname: Iniguez
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.forename: Andy An
authors.initials: AA
authors.lastname: Hoang
authors.forename: Monica
authors.initials: M
authors.lastname: Lavian
authors.forename: Xicui
authors.initials: X
authors.lastname: Sun
authors.forename: Diane K
authors.initials: DK
authors.lastname: O'Dowd
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012679:Sense Organs / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D029721:Drosophila Proteins; D009498:Neurotoxins; D018377:Neurotransmitter Agents; C472405:cac protein, Drosophila; D049452:Green Fluorescent Proteins