Computer modeling defines the system driving a constant current crucial for homeostasis in the mammalian cochlea by integrating unique ion transports

DOI Web Site
  • Nin Fumiaki
    Department of Molecular Physiology, Niigata University School of Medicine, Japan
  • Yoshida Takamasa
    Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Japan
  • Murakami Shingo
    Department of Physiology, School of Medicine, Toho University, Japan
  • Ogata Genki
    Department of Molecular Physiology, Niigata University School of Medicine, Japan
  • Uetsuka Satoru
    Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Japan
  • Doi Katsumi
    Department of Otolaryngology, Faculty of Medicine, Kindai University, Japan
  • Sawamura Seishiro
    Department of Molecular Physiology, Niigata University School of Medicine, Japan
  • Inohara Hidenori
    Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Japan
  • Kurachi Yoshihisa
    Division of Molecular and Cellular Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Japan
  • Hibino Hiroshi
    Department of Molecular Physiology, Niigata University School of Medicine, Japan

抄録

<p>The cochlear lateral wall an epithelial-like tissue comprising inner and outer layers maintains +80 mV in endolymph. This endocochlear potential (EP) supports hearing and represents the sum of all membrane potentials across apical and basolateral surfaces of both layers. Underlying extracellular and intracellular [K+] is likely controlled by the "circulation current," which crosses the two layers and unidirectionally flows throughout the cochlea. This idea was conceptually reinforced by our computational model integrating ion channels and transporters; however, contribution of the outer layer's basolateral surface remains unclear. Recent experiments showed that this basolateral surface transports K+ using Na+,K+-ATPases and an unusual characteristic of greater permeability to Na+ than to other ions. To determine whether and how these machineries are involved in the circulation current, we used an in silico approach. In our updated model, the outer layer's basolateral surface was provided with only Na+,K+-ATPases, Na+ conductance, and leak conductance. Under normal conditions, the circulation current was assumed to consist of K+ and be driven predominantly by Na+,K+-ATPases. The model replicated the experimentally measured electrochemical properties in all compartments of the lateral wall, and EP, under normal conditions and during blocking of Na+,K+-ATPases. Therefore, the circulation current across the outer layer's basolateral surface depends primarily on the three ion transport mechanisms. During the blockage, the reduced circulation current partially consisted of transiently evoked Na+ flow via the two conductances. This work defines the comprehensive system driving the circulation current.</p>

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ