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.

Three-dimensional analysis of the heart function and effect cholinergic agonists in the cockroach Gromphadorhina portentosa

“…The ACh effects on the isolated dorsal vessel of G. portentosa agree with reports on other insects (Jones 1974). The increase in cardiac frequency caused by ACh in G. portetosa preparations has also been documented in D. melanogaster (Malloy et al 2016) and P. americana (Miller and Metcalf 1968).…”

Development and evolution of the metazoan heart

“…A caudally located autonomic‐acting myogenic pacemaker is present, containing an ensemble of ion‐channels from which the majority is also found in humans . Neuroregulators also found in vertebrates, such as acetylcholine, serotonin, and norepinephrine, modulate heart rate in larval, pupal, and adult flies . In cephalopods, the systemic heart and the two branchial hearts are similarly under neuroregulatory control, suggestive of common regulatory pathways.…”

“…174 Neuroregulators also found in vertebrates, such as acetylcholine, serotonin, and norepinephrine, modulate heart rate in larval, pupal, and adult flies. 175,176 In cephalopods, the systemic heart and the two branchial hearts are similarly under neuroregulatory control, 177 suggestive of common regulatory pathways. The activity of the heart in other mollusks strongly depends on the function of surrounding organs such as the gut and the excretory system, as well as on muscle activities related to burrowing movements, for example.…”

Optogenetic stimulation of Drosophila heart rate at different temperatures and Ca2+ concentrations

“…; Malloy et al. ), environmental changes (stress, temperature), (de Castro et al. ) as well as developmental abnormalities and cellular regulation of Ca 2+ dynamics (Johnson et al.…”