title: TheIhChannel Gene Promotes Synaptic Transmission and Coordinated Movement inDrosophila melanogaster.
abstract: Hyperpolarization-activated cyclic nucleotide-gated "HCN" channels, which underlie the hyperpolarization-activated current (Ih), 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 ofDrosophila 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 theIhgene. We propose that the presynaptic HCN channel is active under basal conditions and promotes neurotransmission at larval motor terminals. Finally, we demonstrate thatIhpartial 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.
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia Vancouver, BC, Canada.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Hegle
authors.affiliation: Department of Anatomy and Cell Biology, The University of Iowa Iowa City, IA, USA.
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Frank
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia Vancouver, BC, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Berndt
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia Vancouver, BC, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Klose
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia Vancouver, BC, Canada.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Allan
authors.affiliation: Department of Cellular and Physiological Sciences, The University of British Columbia Vancouver, BC, Canada.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Accili
keywords: Drosophila melanogaster; HCN channel; Ih gene; neuromuscular junction; presynaptic mechanisms