title: Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity.
abstract: Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four β2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of β2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing β2 subunits, we generated mice in which the gene encoding β2 was deleted (β2 knockout [KO]). Comparison of proteins from wild-type (WT) and β2 KO mice allowed unambiguous demonstration of the presence of β2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and β2 KO CCs in slices and found that β2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the β2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from β2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of β2 subunits may predispose to burst firing.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Martinez-Espinosa
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gonzalez-Perez
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110 clingle@morpheus.wustl.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lingle
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D019439:Chromaffin Cells / Q000378:metabolism*; D066298:In Vitro Techniques; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D012313:RNA / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D008565:Membrane Proteins; D012313:RNA