title: Fast, but not slow, effects of olivocochlear activation are resistant to apamin.
abstract: Olivocochlear (OC) efferent suppression of auditory-nerve responses comprises a fast effect lasting tens of milliseconds and a slow effect building and decaying over tens of seconds. Both fast and slow effects are mediated by activation of the same alpha 9 nicotinic receptor. We have hypothesized that fast effects are generated at the OC synapse, but that slow effects reflect activation of calcium-activated potassium (K(Ca)) channels by calcium release from the subsurface cisternae on the basolateral wall of the hair cells. We measured in vivo effects of apamin, a blocker of small-conductance (SK) K(Ca) channels, and charybdotoxin, a blocker of large-conductance K(Ca) channels, perfused through scala tympani, on fast and slow effects evoked by electrical stimulation of the OC bundle in anesthetized guinea pigs. Apamin selectively and reversibly reduced slow-effect amplitude without altering fast effects or baseline amplitude of the auditory-nerve response, but only when perfused at concentrations of 100 microM. In contrast, the effects of charybdotoxin were noted at 30 nM, but were not specific, reducing both afferent and efferent responses. The very high concentrations of apamin needed to block efferent effects contrasts with the high sensitivity of isolated hair cells to apamin's block of acetylcholine's effects. The results suggest that in vivo fast OC effects are dominated by a conductance that is not apamin sensitive.
authors.affiliation: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: M C
authors.initials: MC
authors.lastname: Liberman
authors.forename: M C
authors.initials: MC
authors.lastname: Brown
authors.forename: W F
authors.initials: WF
authors.lastname: Sewell
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D001306:Auditory Pathways / Q000187:drug effects* / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009847:Olivary Nucleus / Q000502:physiology*; D012533:Scala Tympani / Q000187:drug effects / Q000502:physiology
chemical_list: D018999:Charybdotoxin; D001030:Apamin