ATP-sensitive K+ channels (Kir6.1/SUR1) regulate gap junctional coupling in cochlear-supporting cells

Alexander Blödow, Daniela Begandt, Almke Bader, Annegret Becker, Alice Burghard, Daniela Kühne, Andrej Kral, Anaclet Ngezahayo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Using the double whole-cell patch-clamp technique, we found that the absence of intracellular ATP led to gap junction uncoupling in cochlear-supporting Hensen cells. The uncoupling was observed as a progressive reduction of the gap junctional electrical conductance from a starting value of approximately 40 nS to less than 0.04 nS within 10–20 min. The conductance rundown was partly avoided by at least 3 mM ATP and completely suppressed by 5 mM ATP or 5ʹ-adenylyl-imidodiphosphate (AMP-PNP), the non-hydrolysable ATP analog, in the pipette filling solution, suggesting that ATP was needed as ligand and not as a hydrolysable energy supplier or substrate for enzymatic reactions. The effect of intracellular ATP was mimicked by the external application of barium, a nonselective blocker of inwardly rectifying K+ (Kir) channels, and glibenclamide, an inhibitor of the ATP-sensitive Kir channels (KATP). Moreover a Ba2+-sensitive whole-cell inward current was observed in absence of internal ATP. We propose that the internal ATP kept the KATP channels in a closed state, thereby maintaining the gap junction coupling of Hensen cells. The immunostaining of guinea pig cochlear tissue revealed for the first time the expression of the KATP channel subunits Kir6.1 and SUR1 in Hensen cells and supported the proposed hypothesis. The results suggest that KATP channels, as regulator of the gap junction coupling in Hensen cells, could be the physiological link between the metabolic state of the supporting cells and K+ recycling in the organ of Corti.

Original languageEnglish
Pages (from-to)1215-1222
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume468
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016
Externally publishedYes

Keywords

  • ATP-sensitive K+ channels
  • Cochlea
  • Double whole-cell patch-clamp
  • Gap junction
  • Hensen cells
  • Kir6.1
  • SUR1

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