Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2017.00041
Keywords
Ih gene; HCN channel; neuromuscular junction; presynaptic mechanisms; Drosophila melanogaster
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Funding
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- NIH [NS062738]
- Department of Anatomy and Cell Biology, University of Iowa
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Hyperpolarization-activated cyclic nucleotide-gated HCN channels, which underlie the hyperpolarization-activated current (I-h), have been proposed to play diverse roles in neurons. The presynaptic HCN channel is thought to both promote and inhibit neurotransmitter release from synapses, depending upon its interactions with other presynaptic ion channels. In larvae of Drosophila melanogaster, inhibition of the presynaptic HCN channel by the drug ZD7288 reduces the enhancement of neurotransmitter release at motor terminals by serotonin but this drug has no effect on basal neurotransmitter release, implying that the channel does not contribute to firing under basal conditions. Here, we show that genetic disruption of the sole HCN gene (Ih) reduces the amplitude of the evoked response at the neuromuscular junction (NMJ) of third instar larvae by decreasing the number of released vesicles. The anatomy of the (NMJ) is not notably affected by disruption of the Ih gene. We propose that the presynaptic HCN channel is active under basal conditions and promotes neurotransmission at larval motor terminals. Finally, we demonstrate that Ih partial loss-of-function mutant adult flies have impaired locomotion, and, thus, we hypothesize that the presynaptic HCN channel at the (NMJ) may contribute to coordinated movement.
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