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A Rapid Facilitation of Acid-Sensing Ion Channels Current by Corticosterone in Cultured Hippocampal Neurons

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Abstract

Acid-sensing ion channels (ASIC) play an important role in the central neuronal system and excessive activation of ASICs induces neuronal damage. Recent studies show that ASIC1a, a subunit of ASIC, is involved in stress processes but the mechanisms by which ASIC1a is regulated by corticosterone (CORT), a stress-induced hormone, are as yet unelucidated. In the present study, to explore the effects of CORT on ASIC1a in cultured hippocampal neurons, the whole-cell patch clamp technique was used. We present data showing that extracellular application of 1 and 10 μM CORT increase the inward current when solution of pH 6.0 is applied to the exterior of the cell. Moreover, extracellular application of membrane-impermeable CORT-BSA (1 μM) maintains current elevation induced by the action of ASIC1a. However, intracellular application of CORT (1 μM) did not increase ASIC1a current. Subsequent extracellular application of CORT enhanced the amplitude of ASIC1a current. Also, RU38486 (10 μM), an antagonist of nuclear glucocorticoids receptor, did not block an increase of ASIC1a current induced by CORT. In addition, CORT application further resulted in a significant enhancement of ASIC1a current in the presence of phorbol 12-myristate 13-acetate (0.5 μM) or bryostatin1 (1 μM), which are both protein kinase C (PKC) agonists. On the contrary, after pretreatment with GF109203X (3 μM), an antagonist of PKC, CORT did not elevate ASIC1a current. These data indicate that the rapid increase of ASIC1a current induced by CORT may be caused by the activation of corticosteroid receptors found on the cell membranes of hippocampal neurons and it may involve a PKC-dependent mechanism.

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Abbreviations

ASIC:

Acid-sensing ion channel

PKC:

Protein kinase C

PMA:

Phorbol 12-myristate 13-acetate

PcTx1:

Psalmotoxin-1

DMSO:

Dimethyl sulphoxide

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Acknowledgments

This work was supported by project of Chinese National Science and Technology Ministry (2012BAI32B03). We appreciate the contribution of Cathy Derow who carefully revised this manuscript.

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Authors and Affiliations

  1. Medical College, Jianghan University, Wuhan, 430056, China

    Zhe Xiong & YongXun Ai

  2. Center of Reproductive Medicine and Research Institute of Family Planning, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yan Liu, Lian Hu & ChengLiang Xiong

  3. Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Zhe Xiong

  4. Biomedical College, Jianghan University, Wuhan, 430056, China

    BaoMiao Ma

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  1. Zhe Xiong
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  2. Yan Liu
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  3. Lian Hu
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  5. YongXun Ai
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Correspondence to YongXun Ai or ChengLiang Xiong.

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Zhe Xiong and Yan Liu have contributed equally to this study.

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Xiong, Z., Liu, Y., Hu, L. et al. A Rapid Facilitation of Acid-Sensing Ion Channels Current by Corticosterone in Cultured Hippocampal Neurons. Neurochem Res 38, 1446–1453 (2013). https://doi.org/10.1007/s11064-013-1045-9

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  • DOI: https://doi.org/10.1007/s11064-013-1045-9

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