title: The smooth muscle-type β1 subunit potentiates activation by DiBAC4(3) in recombinant BK channels.
abstract: Large-conductance Ca(2+)-activated (BK) channels, expressed in a variety of tissues, play a fundamental role in regulating and maintaining arterial tone. We recently demonstrated that the slow voltage indicator DiBAC4(3) does not depend, as initially proposed, on the β 1 or β 4 subunits to activate native arterial smooth muscle BK channels. Using recombinant mslo BK channels, we now show that the β 1 subunit is not essential to this activation but exerts a large potentiating effect. DiBAC4(3) promotes concentration-dependent activation of BK channels and slows deactivation kinetics, changes that are independent of Ca(2+). Kd values for BK channel activation by DiBAC4(3) in 0 mM Ca(2+) are approximately 20 μM (α) and 5 μM (α+β 1), and G-V curves shift up to -40 mV and -110 mV, respectively. β1 to β2 mutations R11A and C18E do not interfere with the potentiating effect of the subunit. Our findings should help refine the role of the β 1 subunit in cardiovascular pharmacology.
authors.affiliation: Cardiovascular Genetics Center; Institut d'Investigació Biomèdica de Girona (IDIBGI) and School of Medicine; University of Girona (UdG); Girona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosch Calero
authors.affiliation: Cardiovascular Genetics Center; Institut d'Investigació Biomèdica de Girona (IDIBGI) and School of Medicine; University of Girona (UdG); Girona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Selga
authors.affiliation: Cardiovascular Genetics Center; Institut d'Investigació Biomèdica de Girona (IDIBGI) and School of Medicine; University of Girona (UdG); Girona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.affiliation: Cardiovascular Genetics Center; Institut d'Investigació Biomèdica de Girona (IDIBGI) and School of Medicine; University of Girona (UdG); Girona, Spain.
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Scornik
authors.affiliation: Cardiovascular Genetics Center; Institut d'Investigació Biomèdica de Girona (IDIBGI) and School of Medicine; University of Girona (UdG); Girona, Spain.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Pérez
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D021122:Protein Subunits / Q000502:physiology*; D011994:Recombinant Proteins
chemical_list: D001463:Barbiturates; D007555:Isoxazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D011994:Recombinant Proteins; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol
keywords: BK channel opener; BK channels; DiBAC4(3); KCNMA1; KCNMB1; β subunits