Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Christian J Peters
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Shiwei Zhou
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Hannah H Williams
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
Lily Yeh Jan
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
Yuh Nung Jan
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States
While the signals and complexes that coordinate the heartbeat are well established, how the heart maintains its electromechanical rhythm over a lifetime remains an open question with significant implications to human health. Reasoning that this homeostatic challenge confronts all pulsatile organs, we developed a high resolution imaging and analysis toolset for measuring cardiac function in intact, unanesthetized Drosophila melanogaster. We demonstrate that, as in humans, normal aging primarily manifests as defects in relaxation (diastole) while preserving contractile performance. Using this approach, we discovered that a pair of two-pore potassium channel (K2P) subunits, largely dispensable early in life, are necessary for terminating contraction (systole) in aged animals, where their loss culminates in fibrillatory cardiac arrest. As the pumping function of its heart is acutely dispensable for survival, Drosophila represents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging.
