title: BK channels mediate cholinergic inhibition of high frequency cochlear hair cells.
abstract: BACKGROUND
  Outer hair cells are the specialized sensory cells that empower the mammalian hearing organ, the cochlea, with its remarkable sensitivity and frequency selectivity. Sound-evoked receptor potentials in outer hair cells are shaped by both voltage-gated K(+) channels that control the membrane potential and also ligand-gated K(+) channels involved in the cholinergic efferent modulation of the membrane potential. The objectives of this study were to investigate the tonotopic contribution of BK channels to voltage- and ligand-gated currents in mature outer hair cells from the rat cochlea.
  
  
  RESULTS
  Findings In this work we used patch clamp electrophysiology and immunofluorescence in tonotopically defined segments of the rat cochlea to determine the contribution of BK channels to voltage- and ligand-gated currents in outer hair cells. Although voltage and ligand-gated currents have been investigated previously in hair cells from the rat cochlea, little is known about their tonotopic distribution or potential contribution to efferent inhibition. We found that apical (low frequency) outer hair cells had no BK channel immunoreactivity and little or no BK current. In marked contrast, basal (high frequency) outer hair cells had abundant BK channel immunoreactivity and BK currents contributed significantly to both voltage-gated and ACh-evoked K(+) currents.
  
  
  CONCLUSIONS
  Our findings suggest that basal (high frequency) outer hair cells may employ an alternative mechanism of efferent inhibition mediated by BK channels instead of SK2 channels. Thus, efferent synapses may use different mechanisms of action both developmentally and tonotopically to support high frequency audition. High frequency audition has required various functional specializations of the mammalian cochlea, and as shown in our work, may include the utilization of BK channels at efferent synapses. This mechanism of efferent inhibition may be related to the unique acetylcholine receptors that have evolved in mammalian hair cells compared to those of other vertebrates.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Center for Hearing and Balance, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Wersinger
authors.forename: Will J
authors.initials: WJ
authors.lastname: McLean
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fuchs
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: Pyott
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D003051:Cochlea / Q000166:cytology; D006198:Hair Cells, Auditory / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000502:physiology; D007150:Immunohistochemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018678:Cholinergic Agents; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D018999:Charybdotoxin; D001030:Apamin; C064719:iberiotoxin; D000109:Acetylcholine