title: Calcium- and calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea.
abstract: Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37 degrees C, the calcium currents of immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.
authors.affiliation: Center for Hearing and Balance, Departmernt of Otolaryngology, Head and Neck Surgery, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. lgrant11@jhmi.edu
authors.forename: Lisa
authors.initials: L
authors.lastname: Grant
authors.forename: Paul
authors.initials: P
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003051:Cochlea / Q000166:cytology / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004533:Egtazic Acid / Q000494:pharmacology; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D006309:Hearing / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D013696:Temperature; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002147:Calmodulin; D002614:Chelating Agents; D026902:Potassium Channel Blockers; C093712:Cacna1d protein, rat; D002586:Cesium; D004533:Egtazic Acid; D019789:Tetraethylammonium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium