title: BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle.
abstract: The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage-dependent Ca2+ entry in many cell types. The BK channel accessory beta1-subunit promotes channel activation in smooth muscle and is required for proper tone in the vasculature and bladder. However, although BK channels have also been implicated in airway smooth muscle function, their regulation by the beta1-subunit has not been investigated. Utilizing the gene-targeted mice for the beta1-subunit gene, we have investigated the role of the beta1-subunit in tracheal smooth muscle. In mice with the beta1-subunit-knockout allele, BK channel activity was significantly reduced in excised tracheal smooth muscle patches and spontaneous BK currents were reduced in whole tracheal smooth muscle cells. Knockout of the beta1-subunit resulted in an increase in resting Ca2+ levels and an increase in the sustained component of Ca2+ influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the beta1-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the beta1-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the beta1-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca2+ channels. These results indicate that the beta1-subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels.
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
authors.forename: Iurii
authors.initials: I
authors.lastname: Semenov
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jeremiah T
authors.initials: JT
authors.lastname: Herlihy
authors.forename: Robert
authors.initials: R
authors.lastname: Brenner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004594:Electrophysiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D018679:Cholinergic Agonists; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020033:Protein Isoforms; D002217:Carbachol; D002118:Calcium