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Updated: Apr 27, 2026
Visualizing the Beating Heart in Drosophila
Published on: September 28, 2009
Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster
Manuela Santalla1, Carlos A Valverde2, Ezequiel Harnichar2
1Centro de Investigaciones Cardiovasculares, CONICET-La Plata, Facultad de Medicina, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina; Departamento de Ciencias Básicas y Experimentales, Universidad Nacional del Noroeste de Buenos Aires, Pergamino, Buenos Aires, Argentina.
Abstract:
Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.
Insights
Aging impairs heart function, but increasing Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels in fruit flies improved heart rate and contractility, suggesting a therapeutic target for age-related cardiovascular decline.
Area of Science:
- Cardiovascular Physiology
- Aging Research
- Molecular Cardiology
Background:
- Aging leads to cardiovascular dysfunction, including altered contractility and rhythm.
- Drosophila melanogaster serves as a model organism for studying age-related cardiac arrhythmogenic conditions.
- Calcium handling kinase CaMKII is implicated in heart function regulation and arrhythmogenesis.
Purpose of the Study:
- To investigate age-related changes in cardiac calcium handling in Drosophila.
- To elucidate the role of CaMKII in Drosophila heart function during aging.
- To assess the impact of modulating CaMKII activity on cardiac performance.
Main Methods:
- Utilized a genetically engineered Ca2+ indicator to monitor cardiac function in aged Drosophila.
- Performed comparative analysis of CaMKII in Drosophila and humans.
- Administered CaMKII inhibitor (KN-93) and overexpressed CaMKII in fly hearts.
Main Results:
- Aging resulted in prolonged relaxation, reduced heart rate, and increased arrhythmias.
- CaMKII showed high conservation between Drosophila and humans, with conserved phosphorylation sites.
- CaMKII inhibition decreased heart rate; CaMKII overexpression increased heart rate, reduced arrhythmias, and enhanced calcium handling parameters.
Conclusions:
- CaMKII plays a direct role in regulating Drosophila heart function.
- Increased CaMKII expression may improve cardiac contractility and mitigate age-related dysfunction.
- CaMKII represents a potential therapeutic target for enhancing cardiovascular health during aging.
