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.
Highlights
Voltage-gated calcium channels located in the plasma membrane of nerve terminals are essential for neuronal communication
The data presented here demonstrate that the Cav2-type ␣-1 subunit gene cac encodes voltage-gated calcium channels that mediate Plectreurys toxin II (PLTXII)-sensitive, slow-inactivating calcium currents in pupal neurons and adult antennal lobe projection neurons (PNs)
We show that the activity of presynaptic CAC channels regulates spontaneous, action potential (AP)-independent release of excitatory neurotransmitter at central cholinergic synapses both in pupal cultures and in the adult brain
Summary
Voltage-gated calcium channels located in the plasma membrane of nerve terminals are essential for neuronal communication. They mediate depolarization-induced calcium influx that drives release of neurotransmitter. Presynaptic calcium channels are composed of several different subunits. The ␣1 subunit forms the ion conducting pore that defines many of the functional properties characteristic of distinct channel subtypes (Catterall 2000; Catterall et al 2005). The ␣1 subunit genes are grouped into three families, Cav, Cav, and Cav. Within the Cav family there are three genes (Cav2.1, 2.2, and 2.3) that encode distinct presynaptic calcium channels (Ertel et al 2000).
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