title: β4-subunit increases Slo responsiveness to physiological Ca2+ concentrations and together with β1 reduces surface expression of Slo in hair cells.
abstract: Changing kinetics of large-conductance potassium (BK) channels in hair cells of nonmammalian vertebrates, including the chick, plays a critical role in electrical tuning, a mechanism used by these cells to discriminate between different frequencies of sound. BK currents are less abundant in low-frequency hair cells and show large openings in response to a rise in intracellular Ca(2+) at a hair cell's operating voltage range (spanning -40 to -60 mV). Although the molecular underpinnings of its function in hair cells are poorly understood, it is established that BK channels consist of a pore-forming α-subunit (Slo) and a number of accessory subunits. Currents from the α (Slo)-subunit alone do not show dramatic increases in response to changes in Ca(2+) concentrations at -50 mV. We have cloned the chick β(4)- and β(1)-subunits and show that these subunits are preferentially expressed in low-frequency hair cells, where they decrease Slo surface expression. The β(4)-subunit in particular is responsible for the BK channel's increased responsiveness to Ca(2+) at a hair cell's operating voltage. In contrast, however, the increases in relaxation times induced by both β-subunits suggest additional mechanisms responsible for BK channel function in hair cells.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Bai
authors.forename: Alexei
authors.initials: A
authors.lastname: Surguchev
authors.forename: Dhasakumar
authors.initials: D
authors.lastname: Navaratnam
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D003051:Cochlea / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D006198:Hair Cells, Auditory / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium