Age-related changes in K(v)4/Shal and K(v)1/Shaker expression in Drosophila and a role for reactive oxygen species

Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects K(v)4/Shal and K(v)1/Shaker K(+) channel protein levels in Drosophila. We show that K(v)4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion. In contrast, K(v)1/Shaker protein exhibits a transient increase at 10 days that then stabilizes and eventually declines at 40 days. We present data that begin to show a relationship between reactive oxygen species (ROS), K(v)4/Shal, and locomotor performance. We show that K(v)4/Shal levels are negatively affected by ROS, and that over-expression of Catalase or RNAi knock-down of the ROS-generating enzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase (NOX), can attenuate the loss of K(v)4/Shal protein. Finally, we compare levels of K(v)4.2 and K(v)4.3 in the hippocampus, olfactory bulb, cerebellum, and motor cortex of mice aged 6 weeks and 1 year. While there was no global decline in K(v)4.2/4.3 that parallels what we report in Drosophila, we did find that K(v)4.2/4.3 are differentially affected in various brain regions; this survey of changes may help inform mammalian studies that examine neuronal function with age.