The ATP-sensitive potassium (K ATP ) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman

The homeobox transcription factor Tinman plays an important role in the initiation of heart development. Later functions of Tinman, including the target genes involved in cardiac physiology, are less well studied. We focused on thedSUR gene, which encodes an ATP-binding cassette transmembrane protein that is expressed in the heart. Mammalian SUR genes are associated with KATP (ATP-sensitive potassium) channels, which are involved in metabolic homeostasis. We provide experimental evidence that Tinman directly regulatesdSUR expression in the developing heart. We identified acis -regulatory element in the first intron ofdSUR , which contains Tinman consensus binding sites and is sufficient for faithfuldSUR expression in the fly’s myocardium. Site-directed mutagenesis of this element shows that these Tinman sites are critical todSUR expression, and further genetic manipulations suggest that the GATA transcription factor Pannier is synergistically involved in cardiac-restricteddSUR expressionin vivo . Physiological analysis ofdSUR knock-down flies supports the idea that dSUR plays a protective role against hypoxic stress and pacing-induced heart failure. BecausedSUR expression dramatically decreases with age, it is likely to be a factor involved in the cardiac aging phenotype ofDrosophila .dSUR provides a model for addressing how embryonic regulators of myocardial cell commitment can contribute to the establishment and maintenance of cardiac performance.