title: ATP-sensitive K(+) channels (Kir6.1/SUR1) regulate gap junctional coupling in cochlear-supporting cells.
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 5'-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 Ba(2+)-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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery and Communication Disorders, HELIOS-Klinikum Pirna, Pirna, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Blödow
authors.affiliation: Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419, Hannover, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Begandt
authors.affiliation: Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419, Hannover, Germany.
authors.forename: Almke
authors.initials: A
authors.lastname: Bader
authors.affiliation: Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419, Hannover, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Becker
authors.affiliation: Institute of Audioneurotechnology and Department of Experimental Otology, ENT Clinics, Hannover Medical University, Hannover, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Burghard
authors.affiliation: Institute of Audioneurotechnology and Department of Experimental Otology, ENT Clinics, Hannover Medical University, Hannover, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kühne
authors.affiliation: Institute of Audioneurotechnology and Department of Experimental Otology, ENT Clinics, Hannover Medical University, Hannover, Germany.|Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Kral
authors.affiliation: Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419, Hannover, Germany. ngezahayo@biophysik.uni-hannover.de.|Center for Systems Neuroscience, Hannover, Germany. ngezahayo@biophysik.uni-hannover.de.
authors.forename: Anaclet
authors.initials: A
authors.lastname: Ngezahayo
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D054086:KATP Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D064233:Sulfonylurea Receptors / Q000378:metabolism*
chemical_list: D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; C092520:uK-ATP-1 potassium channel; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D011188:Potassium; D005905:Glyburide
keywords: ATP-sensitive K+ channels; Cochlea; Double whole-cell patch-clamp; Gap junction; Hensen cells; Kir6.1; SUR1