title: Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons.
abstract: The L-type Ca2+channel Cav1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving β-adrenergic receptors (βARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser1928in Cav1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser1928is not required for regulation of cardiac Cav1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Cav1.2 and enhancement of its activity by the β2-adrenergic receptor (β2AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Cav1.2 by PKA in cardiomyocytes and hippocampal neurons.
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Patriarchi
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Price
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Matt
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Boram
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Nieves-Cintrón
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Olivia R
authors.initials: OR
authors.lastname: Buonarati
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Chowdhury
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Nanou
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nystoriak
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
authors.affiliation: Department of Pharmacology and Toxicology, Technical University of Munich, D-80802 Munich, Germany.
authors.forename: Montatip
authors.initials: M
authors.lastname: Poomvanicha
authors.affiliation: Department of Pharmacology and Toxicology, Technical University of Munich, D-80802 Munich, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616-8636, USA. mfnavedo@ucdavis.edu jwhell@ucdavis.edu.
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Navedo
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA. mfnavedo@ucdavis.edu jwhell@ucdavis.edu.|Department of Pharmacology, University of California, Davis, CA 95616-8636, USA.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D007093:Imidazoles; C419385:L-type calcium channel alpha(1C); D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D012694:Serine; C026777:ICI 118551; C049763:CGP 20712A; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol