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Oxidation of a potassium channel causes progressive sensory function loss during aging

Nature Neuroscience volume 12, pages 611–617 (2009)Cite this article

Abstract

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.

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Figure 1: KVS-1 channels expressed in mammalian cells are susceptible to redox modulation.
Figure 2: Cys113 mediates redox modulation of KVS-1.
Figure 3: Protected chemosensory function in C113S worms.
Figure 4: Chemosensory loss is lessened in C113S worms during aging.
Figure 5: KVS-1 conducts the A-type current in ASER neurons.
Figure 6: Native KVS-1 currents are modified by oxidizing agents.
Figure 7: Native KVS-1 currents are modified by endogenous ROS.

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Acknowledgements

We thank S. Mitani (Tokyo Women's Medical University School of Medicine) for the tm2034 strain, O. Hobert (Columbia University) for the Pgcy-5::GFP construct and the C. elegans Knockout Consortium for the TJ1052 strain. We thank A. Jauregui and M. Barr for their help with the average speed measurements, and J. Lenard, G. Abbott and L. Runnels for critical reading of the manuscript. This work was supported by a US National Institutes of Health grant (R01GM68581) to F.S.

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  1. Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA

    Shi-Qing Cai & Federico Sesti

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S.-Q.C. and F.S. designed research, performed research and analyzed data. F.S. wrote the manuscript.

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Correspondence to Federico Sesti.

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Cai, SQ., Sesti, F. Oxidation of a potassium channel causes progressive sensory function loss during aging. Nat Neurosci 12, 611–617 (2009). https://doi.org/10.1038/nn.2291

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