Tamoxifen inhibits BK channels in chick cochlea without alterations in voltage-dependent activation
Open Access
- 1 July 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 297 (1), C75-C85
- https://doi.org/10.1152/ajpcell.00659.2008
Abstract
Large-conductance, Ca2+-activated, and voltage-gated potassium channels (BK, BKCa, or Maxi-K) play an important role in electrical tuning in nonmammalian vertebrate hair cells. Systematic changes in tuning frequency along the tonotopic axis largely result from variations in BK channel kinetics, but the molecular changes underpinning these functional variations remain unknown. Auxiliary β1 have been implicated in low-frequency tuning at the cochlear apex because these subunits dramatically slow channel kinetics. Tamoxifen (Tx), a (xeno)estrogen compound known to activate BK channels through the β-subunit, was used to test for the functional presence of β1. The hypotheses were that Tx would activate the majority of BK channels in hair cells from the cochlear apex due to the presence of β1 and that the level of activation would exhibit a tonotopic gradient following the expression profile of β1. Outside-out patches of BK channels were excised from tall hair cells along the apical half of the chicken basilar papilla. In low-density patches, single-channel conductance was reduced and the averaged open probability was unaffected by Tx. In high-density patches, the amplitude of ensemble-averaged BK current was inhibited, whereas half-activation potential and activation kinetics were unaffected by Tx. In both cases, no tonotopic Tx-dependent activation of channel activity was observed. Therefore, contrary to the hypotheses, electrophysiological assessment suggests that molecular mechanisms other than auxiliary β-subunits are involved in generating a tonotopic distribution of BK channel kinetics and electric tuning in chick basilar papilla.Keywords
This publication has 61 references indexed in Scilit:
- Structural determinants of monohydroxylated bile acids to activate β1 subunit-containing BK channelsJournal of Lipid Research, 2008
- Resveratrol attenuates early pyramidal neuron excitability impairment and death in acute rat hippocampal slices caused by oxygen-glucose deprivationExperimental Neurology, 2008
- Estrogen receptor β protects against acoustic trauma in miceJCI Insight, 2008
- The second transmembrane domain of the large conductance, voltage‐ and calcium‐gated potassium channel β1 subunit is a lithocholate sensorFEBS Letters, 2008
- Depletion of membrane cholesterol eliminates the Ca2+‐activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytesThe Journal of Physiology, 2007
- The Role of BKCa Channels in Electrical Signal Encoding in the Mammalian Auditory PeripheryJournal of Neuroscience, 2006
- Developmental expression of Cav1.3 (α1d) calcium channels in the mouse inner earDevelopmental Brain Research, 2004
- Variation in Large‐Conductance, Calcium‐Activated Potassium Channels from Hair Cells Along the Chicken Basilar PapillaThe Journal of Physiology, 2003
- hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large‐conductance calcium‐activated potassium channel β subunit familyFEBS Letters, 2000
- MECHANISMS OF HAIR CELL TUNINGAnnual Review of Physiology, 1999