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NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K+ transport that controls the electrochemical properties in the mammalian cochlea

  • Sensory physiology
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Abstract

Unidirectional K+ transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K+] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K+ diffusion potential elicited by a large K+ gradient across the syncytial apical surface. The K+ gradient depends on the unidirectional K+ transport driven by Na+,K+-ATPases on the basolateral surface of each layer and the concomitant Na+,K+,2Cl−-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na+,K+-ATPases in the syncytial layer also seem to participate in the K+ transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K+] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na+,K+-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K+] of the IS. Consequently, the K+ gradient decreased and the ISP declined. These observations resembled those when the marginal cells’ Na+,K+-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K+ transport.

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Acknowledgments

We thank Dr. Samuel Lagier (University of Geneva) and Dr. Adria LeBoeuf (University of Lausanne) for their critical reading of the text. This work is supported by following research grants and funds: Grant-in-Aid for Scientific Research B 25293058 (to HH), Grant-in-Aid for Scientific Research on Innovative Areas 22136002 (to YK) and 25136704 (to FN), Grant-in-Aid for Young Scientists B 25870248(to FN), Grant-in-Aid for Research Activity Start-up Research Project 25893075 (to GO), the Global COE Program “in silico medicine” at Osaka University (to YK), and a grant for “Research and Development of Next-Generation Integrated Life Simulation Software” (to YK) from the Ministry of Education, Culture, Sport, Science and Technology of Japan, the Senri Life Science Foundation (to HH), the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (to HH), the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to HH), the NOVARTIS Foundation (Japan) for the Promotion of Science (to HH), the Takeda Science Foundation (to HH and FN), the Naito Foundation (to HH), Yujin Memorial Grant (to HH), the Salt Science Research Foundation (to FN), and Grant for Promotion of Niigata University Research Projects (24A006) (to HH).

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None.

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The experiments comply with the current laws of Japan.

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Authors and Affiliations

  1. Department of Molecular Physiology, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan

    Takamasa Yoshida, Fumiaki Nin, Genki Ogata, Satoru Uetsuka & Hiroshi Hibino

  2. Center for Transdisciplinary Research, Niigata University, Niigata, Japan

    Takamasa Yoshida, Fumiaki Nin, Genki Ogata, Satoru Uetsuka & Hiroshi Hibino

  3. Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takamasa Yoshida & Shizuo Komune

  4. Department of Otorhinolaryngology–Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Japan

    Satoru Uetsuka, Tadashi Kitahara & Hidenori Inohara

  5. Department of Otorhinolaryngology–Head and Neck Surgery, Nara Medical University, Kashihara, Japan

    Tadashi Kitahara

  6. Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan

    Kohei Akazawa

  7. Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, and The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Japan

    Yoshihisa Kurachi

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  1. Takamasa Yoshida
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  2. Fumiaki Nin
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  3. Genki Ogata
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  4. Satoru Uetsuka
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  9. Yoshihisa Kurachi
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  10. Hiroshi Hibino
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Correspondence to Hiroshi Hibino.

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Yoshida, T., Nin, F., Ogata, G. et al. NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K+ transport that controls the electrochemical properties in the mammalian cochlea. Pflugers Arch - Eur J Physiol 467, 1577–1589 (2015). https://doi.org/10.1007/s00424-014-1597-9

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