From action potential to contraction: Neural control and excitation–contraction coupling in larval muscles of Drosophila

Peron, Samantha; Zordan, Mauro Agostino; Magnabosco, Anna; Reggiani, Carlo; Megighian, Aram

doi:10.1016/j.cbpa.2009.04.626

Cited by 30 publications

(29 citation statements)

References 121 publications

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“…One possible model is that DPKQDFMRFamide activates the PTX-sensitive G-protein, whose subunits act directly on the L-type channels to elicit Ca 2+ influx, possibly shifting their activation voltage. Peptide-induced Ca 2+ influx would induce contraction via calcium-induced release of calcium from the sarcoplasmic reticulum (Sullivan et al, 2000;Peron et al, 2009;Ushio et al, 1993). G βγ subunits have been shown to act directly on N-, P/Q-, R-and T-type calcium channels (Herlitze et al, 1996;Ikeda, 1996;Wolfe et al, 2003) but they inhibit these channels rather than excite them.…”

Section: Research Articlementioning

confidence: 99%

Mode of Action of aDrosophilaFMRFamide in Inducing Muscle Contraction

Milakovic

Ormerod

Klose

et al. 2014

Journal of Experimental Biology

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Drosophila melanogaster is a model system for examining the mechanisms of action of neuropeptides. DPKQDFMRFamide was previously shown to induce contractions in Drosophila body wall muscle fibres in a Ca 2+ -dependent manner. The present study examined the possible involvement of a G-protein-coupled receptor and second messengers in mediating this myotropic effect after removal of the central nervous system. DPKQDFMRFamide-induced contractions were reduced by 70% and 90%, respectively, in larvae with reduced expression of the Drosophila Fmrf receptor (FR) either ubiquitously or specifically in muscle tissue, compared with the response in control larvae in which expression was not manipulated. No such effect occurred in larvae with reduced expression of this gene only in neurons. The myogenic effects of DPKQDFMRFamide do not appear to be mediated through either of the two Drosophila myosuppressin receptors (DmsR-1 and DmsR-2). DPKQDFMRFamide-induced contractions were not reduced in Ala1 transgenic flies lacking activity of calcium/calmodulin-dependent protein kinase (CamKII), and were not affected by the CaMKII inhibitor KN-93. Peptide-induced contractions in the mutants of the phospholipase C-β (PLCβ) gene (norpA larvae) and in IP 3 receptor mutants were similar to contractions elicited in control larvae. The peptide failed to increase cAMP and cGMP levels in Drosophila body wall muscles. Peptide-induced contractions were not potentiated by 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, and were not antagonized by inhibitors of cAMP-dependent or cGMPdependent protein kinases. Additionally, exogenous application of arachidonic acid failed to induce myogenic contractions. Thus, DPKQDFMRFamide induces contractions via a G-protein coupled FMRFamide receptor in muscle cells but does not appear to act via cAMP, cGMP, IP 3 , PLC, CaMKII or arachidonic acid.

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Section: Research Articlementioning

confidence: 99%

Mode of Action of aDrosophilaFMRFamide in Inducing Muscle Contraction

Milakovic

Ormerod

Klose

et al. 2014

Journal of Experimental Biology

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“…Drosophila melanogaster are being used for investigating gene mutations that are responsible for disease states in other animals including humans (Bier and Bodmer, 2004;Peron et al, 2009). Now various diseases are being induced in this tractable genetic organism (Dowse et al, 1995;Johnson et al, 1998;Ganetzky, 2000;Bier and Bodmer, 2004;Ocorr et al, 2007a, b) and with the hope that in time gene therapy can be tested for regain of normal function.…”

Section: Introductionmentioning

confidence: 99%

<em>Drosophila melanogaster</em> for Physiological Studies

Cooper

Rymond

Ward

et al. 2009

JoVE

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We present various methods to record cardiac function in the larval Drosophila. The approaches allow heart rate to be measured in unrestrained and restrained whole larvae. For direct control of the environment around the heart another approach utilizes the dissected larvae and removal of the internal organs in order to bathe the heart in desired compounds. The exposed heart also allows membrane potentials to be monitored which can give insight of the ionic currents generated by the myocytes and for electrical conduction along the heart tube. These approaches have various advantages and disadvantages for future experiments that are discussed. The larval heart preparation provides an additional model besides the Drosophila skeletal NMJ to investigate the role of intracellular calcium regulation on cellular function. Learning more about the underlying ionic currents that shape the action potentials in myocytes in various species, one can hope to get a handle on the known ionic dysfunctions associated to specific genes responsible for various diseases in mammals.

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“…Reduction in the L-type current is more than just a decrease in a depolarizing current, because Ca 2+ entering the cell during the action potential is essential not only for maintaining depolarization, but also for excitation-contraction coupling [36] and replenishment of Ca 2+ stores in the sarcoplasmic reticulum (SR). In the presence of a L-type Ca 2+ channel blocker, reduced influx of Ca 2+ through these channels will lower the overall Ca 2+ load in the lumen during the action potential, which can itself compromise the contraction directly or via reduced Ca 2+ induced Ca 2+ release.…”

Section: Discussionmentioning

confidence: 99%

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

Frolov

Singh

2012

PLoS ONE

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Recent findings suggest that modulation of ion channels might be implicated in some of the clinical effects of coxibs, selective inhibitors of cyclooxygenase-2 (COX-2). Celecoxib and its inactive analog 2,5-dimethyl-celecoxib, but not rofecoxib, can suppress or augment ionic currents and alter functioning of neurons and myocytes. To better understand these unexpected effects, we have recently investigated the mechanism of inhibition of human Kv2.1 channels by a highly selective COX-2 inhibitor SC-791. In this study we have further explored the SC-791 action on ion channels and heartbeat in Drosophila, which lacks cyclooxygenases and thus can serve as a convenient model to study COX-2-independent mechanisms of coxibs. Using intracellular recordings in combination with a pharmacological approach and utilizing available Drosophila mutants, we found that SC-791 inhibited voltage-activated K+ and L-type Ca2+ channels in larval body-wall muscles and reduced heart rate in a concentration-dependent manner. Unlike celecoxib and several other K+ channel blockers, SC-791 did not induce arrhythmia. Instead, application of SC-791 resulted in a dramatic slowing of contractions and, at higher concentrations, in progressively weaker contractions with gradual cessation of heartbeat. Isradipine, a selective blocker of L-type Ca2+ channels, showed a similar pattern of heart arrest, though no prolongation of contractions was observed. Ryanodine was the only channel modulating compound of those tested additionally that was capable of slowing contractions. Like SC-791, ryanodine reduced heart rate without arrhythmia. However, it could not stop heartbeat completely even at 500 µM, the highest concentration used. The magnitude of heart rate reduction, when SC-791 and ryanodine were applied together, was smaller than expected for independent mechanisms, raising the possibility that SC-791 might be interfering with excitation-contraction coupling in Drosophila heart.

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From action potential to contraction: Neural control and excitation–contraction coupling in larval muscles of Drosophila

Cited by 30 publications

References 121 publications

Mode of Action of aDrosophilaFMRFamide in Inducing Muscle Contraction

Mode of Action of aDrosophilaFMRFamide in Inducing Muscle Contraction

<em>Drosophila melanogaster</em> for Physiological Studies

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

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