The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion

BMC Physiol. 2016 Aug 11;17(1):1. doi: 10.1186/s12899-016-0024-1.

Abstract

Background: Disturbance of acid-base balance in the inner ear is known to be associated with hearing loss in a number of conditions including genetic mutations and pharmacologic interventions. Several previous physiologic and immunohistochemical observations lead to proposals of the involvement of acid-base transporters in stria vascularis.

Results: We directly measured acid flux in vitro from the apical side of isolated stria vascularis from adult C57Bl/6 mice with a novel constant-perfusion pH-selective self-referencing probe. Acid efflux that depended on metabolism and ion transport was observed from the apical side of stria vascularis. The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694, b) by inhibition of Na,2Cl,K-cotransporter (NKCC1) by bumetanide, and c) by the likely inhibition of HCO3/anion exchange by DIDS. By contrast, the acid flux was increased by inhibition of gastric H,K-ATPase (SCH28080) but was not affected by an inhibitor of vH-ATPase (bafilomycin). K flux from stria vascularis was reduced less than 5 % by SCH28080.

Conclusions: These observations suggest that stria vascularis may be an important site of control of cochlear acid-base balance and demonstrate a functional role of several acid-base transporters in stria vascularis, including basolateral H,K-ATPase and apical Na,H-exchange. Previous suggestions that H secretion is mediated by an apical vH-ATPase and that basolateral H,K-ATPase contributes importantly to K secretion in stria vascularis are not supported. These results advance our understanding of inner ear acid-base balance and provide a stronger basis to interpret the etiology of genetic and pharmacologic cochlear dysfunctions that are influenced by endolymphatic pH.

Keywords: Acid–base balance; Endolymph; Hydrogen ion secretion; Inner ear; Ion-selective self-referencing electrode; Potassium secretion; Stria vascularis.

MeSH terms

  • Acid-Base Equilibrium*
  • Animals
  • Endolymph / metabolism*
  • Female
  • H(+)-K(+)-Exchanging ATPase / metabolism*
  • Hydrogen-Ion Concentration
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Potassium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Stria Vascularis / enzymology
  • Stria Vascularis / metabolism*

Substances

  • H(+)-K(+)-Exchanging ATPase
  • Sodium-Potassium-Exchanging ATPase
  • Potassium