These findings explain the pathogenesis in a subset of patients with severe hypertension and implicate loss of K(+) channel selectivity in constitutive aldosterone production.

No abstract

Background: DPP6, a transmembrane protein with a large extracellular domain, is an auxiliary subunit of Kv4.2 potassium channels. Results: The extracellular domain is required for DPP6 export from the ER while intracellular domains impart the functional impact on Kv4.2. Conclusion: Different DPP6 domains are responsible for its localization and function. Significance: Understanding DPP6 function may provide insight into its role in neuronal development and disease.

Adult Drosophila melanogaster has long been a popular model for learning and memory studies. Now the larval stage of the fruit fly is also being used in an increasing number of classical conditioning studies. In this study, we employed heat shock as a novel negative reinforcement for larvae and obtained high learning scores following just one training trial. We demonstrated heat-shock conditioning in both reciprocal and non-reciprocal paradigms and observed that the time window of association for the odor and heat shock reinforcement is on the order of a few minutes. This is slightly wider than the time window for electroshock conditioning reported in previous studies, possibly due to lingering effects of the high temperature. To test the utility of this simplified assay for the identification of new mutations that disrupt learning, we examined flies carrying mutations in the dnc gene. While the sensitivity to heat shock, as tested by writhing, was similar for wild type and dnc homozygotes, dnc mutations strongly diminished learning. We confirmed that the learning defect in dnc flies was indeed due to mutation in the dnc gene using non-complementation analysis. Given that heat shock has not been employed as a reinforcement for larvae in the past, we explored learning as a function of heat shock intensity and found that optimal learning occurred around 41 °C, with higher and lower temperatures both resulting in lower learning scores. In summary, we have developed a very simple, robust paradigm of learning in fruit fly larvae using heat shock reinforcement.