ATP hydrolysis is critically required for function of CaV1.3 channels in cochlear inner hair cells via fueling Ca2+ clearance.
Sound encoding is mediated by Ca(2+) influx-evoked release of glutamate at the ribbon synapse of inner hair cells. Here we studied the role of ATP in this process focusing on Ca(2+) current through CaV1.3 channels and Ca(2+) homeostasis in mouse inner hair cells. Patch-clamp recordings and Ca(2+) imaging demonstrate that hydrolyzable ATP is essential to maintain synaptic Ca(2+) influx in inner hair cells via fueling Ca(2+)-ATPases to avoid an increase in cytosolic [Ca(2+)] and subsequent Ca(2+)/calmodulin-dependent inactivation of CaV1.3 channels.
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany, International Max-Planck Research School Neuroscience, Göttingen Graduate School for Neuroscience and Molecular Biosciences, and.
Simon
S
Weiler
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany, International Max-Planck Research School Molecular Biology, Göttingen Graduate School for Neuroscience and Molecular Biosciences, University of Göttingen, 37077 Göttingen, Germany, and.
Stefanie
S
Krinner
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany, Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany.
Aaron B
AB
Wong
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany, International Max-Planck Research School Neuroscience, Göttingen Graduate School for Neuroscience and Molecular Biosciences, and International Max-Planck Research School Molecular Biology, Göttingen Graduate School for Neuroscience and Molecular Biosciences, University of Göttingen, 37077 Göttingen, Germany, and Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany tpangrs@gwdg.de tmoser@gwdg.de.
Tobias
T
Moser
InnerEarLab, Department of Otolaryngology, University Medical Center Göttingen, 37099 Göttingen, Germany, Collaborative Research Center 889, University of Göttingen, 37099 Göttingen, Germany tpangrs@gwdg.de tmoser@gwdg.de.
Tina
T
Pangršič
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006868:Hydrolysis; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D013569:Synapses / Q000378:metabolism*
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D000255:Adenosine Triphosphate; D002118:Calcium
calcium; calmodulin; channel; hair cell; inactivation; ribbon synapse