Modulation of the cardiac pacemaker of Drosophila : cellular mechanisms

Abstract

The myogenic cardiac pacemaker of Drosophila melanogaster responds to a range of neurotransmitters and hormones by adjusting heart rate. These cardioactive substances ultimately affect the activity of ion channels comprising the pacemaker. We report here work utilizing genetic variants and pharmacological tools to explore a subset of possible mechanisms for this cellular signaling, specifically: receptors, cAMP, cGMP, G proteins, and calcium. We found that alpha(1) adrenergic and 5-hydroxytryptamine(2) (5-HT(2)) receptors are critical components of mediating modulation of heart rate. There was no evidence that the cAMP system is part of the modulatory mechanism. cGMP is likely to be integral to one active pathway, as non-hydrolyzable forms of this cyclic nucleotide increase heart rate, and flies bearing the mutation sitter, a recessive allele of the foraging gene, which encodes a cGMP-dependent kinase, have tachycardia. Heart rhythm is affected by pertussis toxin and by agonists and antagonists of both alpha(1) adrenergic and 5-HT(2) receptors; this suggests involvement of two different types of G proteins. The l(4)16/ciD line, containing a mutation in CaM kinase II, eliminates pacemaker responsiveness to serotonin but is without effect on norepinephrine sensitivity. This result is the same as that for the CaM kinase II enzyme inhibitor KN-93. This work establishes a framework for further investigations into the control of the cardiac pacemaker, and expands the applicability of the Drosophila heart model.

Environment Exploration and Colonization Behavior of the Pea Aphid Associated with the Expression of the foraging Gene

“…As our results were obtained using whole aphid body and not only head, which is the control center of the behavior, a direct correlation between Apfor and the aphid behavior could not be inferred. Indeed, the for gene has also been shown in Drosophila to be implicated in other physiological processes such as cristal cells formations [26] or modulation of the cardiac rythm in Drosophila [27]. We thus performed measurements of the PKG enzyme activity in whole bodies and in heads of the different behavioral variants.…”

Age-dependent electrical and morphological remodeling of the Drosophila heart caused by hERG/seizure mutations

“…Both dilated and restricted cardiomyopathies have been described by us and others in the fly heart and have been linked to mutations in homologous genes with similar effects in human heart [17,19–22]. In addition, there is evidence of channelopathies in the fly heart that are reminiscent of what is observed in human patients [6,14,16,23–25]. For example, we have previously shown that the KCNQ K + channel, which underlies a slow outward rectifying current in human myocardial cells (I Ks ), also functions in the fly heart and that mutations in this channel contribute to heart arrhythmias [16], as they do humans ([26–28]).…”

“…Despite the structural differences, a number of studies indicate that there are significant functional similarities between the fly and human heart. As in vertebrates, heart function in Drosophila is myogenic [11,12] and its rate can be modulated by neuronal and hormonal input [13,14]. Heart muscle protein composition, as well as muscle function and dysfunction share many similarities to human hearts [15–18].…”

Inhibition of Ion Channels and Heart Beat in Drosophila by Selective COX-2 Inhibitor SC-791

“…The larval heart has a pacemaker region and a non-pacemaking myocardium [25]. Electrical activity in the heart is driven by myogenic pacemaker located in the caudal-most segment of the heart [26].…”