Cai Shi-Qing, Sesti Federico
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, USA.
Nat Neurosci. 2009 May;12(5):611-7. doi: 10.1038/nn.2291. Epub 2009 Mar 29.
Potassium channels are key regulators of neuronal excitability. Here we show that oxidation of the K(+) channel KVS-1 during aging causes sensory function loss in Caenorhabditis elegans and that protection of this channel from oxidation preserves neuronal function. Chemotaxis, a function controlled by KVS-1, was significantly impaired in worms exposed to oxidizing agents, but only moderately affected in worms harboring an oxidation-resistant KVS-1 mutant (C113S). In aging C113S transgenic worms, the effects of free radical accumulation were significantly attenuated compared to those in wild type. Electrophysiological analyses showed that both reactive oxygen species (ROS) accumulation during aging and acute exposure to oxidizing agents acted primarily to alter the excitability of the neurons that mediate chemotaxis. Together, these findings establish a pivotal role for ROS-mediated oxidation of voltage-gated K(+) channels in sensorial decline during aging in invertebrates.
钾通道是神经元兴奋性的关键调节因子。我们在此表明，衰老过程中钾离子通道KVS-1的氧化会导致秀丽隐杆线虫的感觉功能丧失，而保护该通道免受氧化可保留神经元功能。趋化性是一种受KVS-1控制的功能，在暴露于氧化剂的线虫中显著受损，但在携带抗氧化KVS-1突变体（C113S）的线虫中仅受到中度影响。在衰老的C113S转基因线虫中，与野生型相比，自由基积累的影响显著减弱。电生理分析表明，衰老过程中活性氧（ROS）的积累以及急性暴露于氧化剂主要作用于改变介导趋化性的神经元的兴奋性。这些发现共同确立了ROS介导的电压门控钾通道氧化在无脊椎动物衰老过程中的感觉功能衰退中起关键作用。
