Presynaptic function of the voltage-gated calcium channel DmCa1D in Drosophila larval motoneurons
Date issued
Authors
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
License
Abstract
Voltage-gated calcium-channels (VGCCs) are indispensable for neuronal information processing. The different functions mediated by VGCCs are dependent on their conductance, activation and inactivation kinetics and their location in different compartments. These include exocytosis of synaptic vesicles from presynaptic terminals, generating of plateau potentials, modifications of action potential-shape, frequency, and propagation along the axon, as well as amplification of postsynaptic potential in dendrites. In Drosophila there are three different genes for VGCCs: DmCa1D (Cav1), DmCa1A (Cav2) and DmCa1G (Cav3), each of which is homolog to one vertebrate family.
This work addresses the functions of DmCa1D L-type channels in different compartments of larval motoneurons. In collaboration with other members of the Duch lab we show that axonal and dendritic DmCa1D channels increase motoneuron firing rates. Ca2+ influx into motoneuron dendrites may amplify postsynaptic potentials, thus increasing firing rates and burst durations. During high frequency motoneuron firing, Ca2+ influx through axonal DmCa1D channels causes fast de-inactivation of sodium channels via transient BK channel activation, thus shortening the refractory period. Therefore, in Drosophila larvae axonal and dendritic DmCa1D channels enhance motoneuron firing and thus synaptic vesicle release to the muscle. Based on these findings I then focused on the question whether DmCa1D channels may also enhance synaptic vesicle turn-over.
In Drosophila, synaptic vesicle release requires presynaptic Ca2+ influx through DmCa1A channels at active zones. In multiple systems, including the Drosophila neuromuscular junction, the recycling of synaptic vesicles is also affected by Ca2+. I provide evidence that DmCa1D channels mediate presynaptic Ca2+ influx to enhance synaptic vesicle retrieval at larval motoneuron terminals. DmCa1D channels localize to the periactive zone of motoneuron synaptic terminals, but there is no co-localization with the active zone marker Bruchpilot. Localization is in agreement with a potential role in synaptic vesicle endocytosis. This is further supported by increased synaptic depression upon genetic manipulation of presynaptic DmCa1D channels. Moreover, pharmacological blockade of DmCa1D reduces SV endocytosis while exocytosis is likely not affected. In sum, localization of DmCa1D to three different compartments of motoneurons provides three separate mechanisms that cooperatively augment maximum motoneuron firing rates with sustainable information transfer to the muscle.