title: Effects of intracellular stores and extracellular Ca(2+) on Ca(2+)-activated K(+) currents in mature mouse inner hair cells.
abstract: Ca(2+)-activated K(+) currents were studied in inner hair cells (IHCs) of mature mice. I(K,f), the large-conductance Ca(2+)-activated K(+) current (BK) characteristic of mature IHCs, had a fast activation time constant (0.4 ms at -25 mV at room temperature) and did not inactivate during 170 ms. Its amplitude, measured at -25 mV, and activation time constant were similar between IHCs in the apical and basal regions of the cochlea. I(K,f) was selectively blocked by 30 nm IbTx but was unaffected by superfusion of Ca(2+)-free solution, nifedipine or Bay K 8644, excluding the direct involvement of voltage-gated Ca(2+) channels in I(K,f) activation. Increasing the intracellular concentration of the Ca(2+) chelator BAPTA from 0.1 mm to 30 mm reduced the amplitude of I(K,f) at -25 mV and shifted its activation by 37 mV towards more depolarized potentials. A reduction in the size of I(K,f) and a depolarizing shift of its activation were also seen when either thapsigargin and caffeine or ryanodine were added intracellularly, suggesting that I(K,f) is modulated by voltage-dependent release from intracellular Ca(2+) stores. Mature IHCs had a small additional Ca(2+)-activated K(+) current (I(K(Ca))), activated by Ca(2+) flowing through L-type Ca(2+) channels. This current was still present during superfusion of either IbTx (60 nm) or apamin (300 nm) but was abolished in Cs(+)-based intracellular solution or during superfusion of 5 mm TEA, suggesting the presence of an additional BK-channel type. Current clamp experiments at body temperature show that I(K,f), but not I(K(Ca)), is essential for fast voltage responses of mature IHCs.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Corné J
authors.initials: CJ
authors.lastname: Kros
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D007211:Indoles; D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011725:Pyridines; D001030:Apamin; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C064719:iberiotoxin; C061017:linopirdine; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium