title: Pharmacological identification of cholinergic receptor subtypes on Drosophila melanogaster larval heart.
abstract: The Drosophila melanogaster heart is a popular model in which to study cardiac physiology and development. Progress has been made in understanding the role of endogenous compounds in regulating cardiac function in this model. It is well characterized that common neurotransmitters act on many peripheral and non-neuronal tissues as they flow through the hemolymph of insects. Many of these neuromodulators, including acetylcholine (ACh), have been shown to act directly on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the central nervous system (CNS) of vertebrates and at the neuromuscular junctions on skeletal and cardiac tissue. In insects, ACh is the primary excitatory neurotransmitter of sensory neurons and is also prominent in the CNS. A full understanding regarding the regulation of the Drosophila cardiac physiology by the cholinergic system remains poorly understood. Here we use semi-intact D. melanogaster larvae to study the pharmacological profile of cholinergic receptor subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists, nicotine and muscarine both increase HR, while nAChR agonist clothianidin exhibits no significant effect when exposed to an open preparation at concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists increase HR as well but also display capabilities of blocking agonist actions. These results provide evidence that both of these receptor subtypes display functional significance in regulating the larval heart's pacemaker activity.
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA. malloycole@gmail.com.
authors.forename: Cole A
authors.identifier: http://orcid.org/0000-0003-3622-798X
authors.initials: CA
authors.lastname: Malloy
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Ritter
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA.
authors.forename: Connor
authors.initials: C
authors.lastname: English
authors.affiliation: Department of Biology and Center for Muscle Biology, University of Kentucky, 675 Rose Street, Lexington, KY, 40506-0225, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cooper
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007814:Larva / Q000187:drug effects / Q000502:physiology; D009116:Muscarine / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D029721:Drosophila Proteins; D011950:Receptors, Cholinergic; D009538:Nicotine; D009116:Muscarine; D000109:Acetylcholine
keywords: Acetylcholine; Drosophila melanogaster; Heart; Muscarinic receptor; Nicotinic receptor; Pharmacology