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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 NgezahayoEmail author
Ion channels, receptors and transporters

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.

Keywords

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

Notes

Acknowledgments

The authors thank Ina G. Siller for the help with imaging the cochlear slides. We thank Dr. Kathrin Rübensam, ZTL, MH Hannover, and Dr. Henning Vogt, HNO-Klinik, MH Hannover for their kind help with the animals.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Alexander Blödow
    • 1
  • Daniela Begandt
    • 2
  • Almke Bader
    • 2
  • Annegret Becker
    • 2
  • Alice Burghard
    • 3
  • Daniela Kühne
    • 3
  • Andrej Kral
    • 3
    • 4
  • Anaclet Ngezahayo
    • 2
    • 4
    Email author
  1. 1.Department of Otolaryngology, Head and Neck Surgery and Communication DisordersHELIOS-Klinikum PirnaPirnaGermany
  2. 2.Institute of BiophysicsLeibniz University HannoverHannoverGermany
  3. 3.Institute of Audioneurotechnology and Department of Experimental Otology, ENT ClinicsHannover Medical UniversityHannoverGermany
  4. 4.Center for Systems NeuroscienceHannoverGermany

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