Tamoxifen inhibits BK channels in chick cochlea without alterations in voltage-dependent activation.
Large-conductance, Ca(2+)-activated, and voltage-gated potassium channels (BK, BK(Ca), 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 beta(1) 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 beta-subunit, was used to test for the functional presence of beta(1). The hypotheses were that Tx would activate the majority of BK channels in hair cells from the cochlear apex due to the presence of beta(1) and that the level of activation would exhibit a tonotopic gradient following the expression profile of beta(1). 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 beta-subunits are involved in generating a tonotopic distribution of BK channel kinetics and electric tuning in chick basilar papilla.
Kresge Hearing Research Institute, Univ. of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-5616, USA.
Mingjie
M
Tong
R Keith
RK
Duncan
D000818:Animals; D000831:Animals, Newborn; D002645:Chickens; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen