Lack of p11 Expression Facilitates Acidity-Sensing Function of TASK1 Channels in Mouse Adrenal Medullary Cells

FASEB J. 2019 Jan;33(1):455-468. doi: 10.1096/fj.201800407RR. Epub 2018 Jul 12.

Abstract

External acidity induces catecholamine secretion by inhibiting TASK1-like channels in rat adrenal medullary (AM) cells. TASK channels can function as a heteromer or homomer in the TASK subfamily. In this study, we elucidate the molecular identity of TASK1-like channels in mouse AM cells using gene knockout. Genetic deletion of TASK1, but not TASK3, abolished the depolarizing inward current and catecholamine secretion in response to acidity, whereas it did not affect the resting current level. Immunocytochemistry revealed that AM cells exhibited predominantly TASK1-like and little TASK3-like immunoreactivity. A proximity ligation assay showed that TASK1/3 heteromeric channels were not formed in AM cells or PC12 cells. However, the exogenous expression of p11 in PC12 cells resulted in the heteromeric formation of TASK isoforms, which were mainly located in the cytoplasm, and p11 was not expressed in rat adrenal medullae or PC12 cells. In AM cells, genetic deletion of TASK1 resulted in enhancement of the immunoreactivity of the TALK2 channel, but not TASK3. The results indicate that TASK1 homomeric channels function as acidity sensors in AM cells, and that function is facilitated by the lack of p11 expression.-Inoue, M., Matsuoka, H., Lesage, F., Harada, K. Lack of p11 expression facilitates acidity-sensing function of TASK1 channels in mouse adrenal medullary cells.

Keywords: ER exit; K channel; chromaffin cell; pH; trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / physiology*
  • Acids / chemistry*
  • Adrenal Medulla / physiology*
  • Animals
  • Annexin A2 / deficiency*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / physiology*
  • PC12 Cells
  • Potassium Channels / physiology*
  • Potassium Channels, Tandem Pore Domain / physiology*
  • Rats
  • S100 Proteins / deficiency*

Substances

  • Acid Sensing Ion Channels
  • Acids
  • Annexin A2
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • S100 Proteins
  • S100 calcium binding protein A10
  • TASK3 protein, mouse
  • potassium channel subfamily K member 3