title: Apocalmodulin itself promotes ion channel opening and Ca(2+) regulation.
abstract: The Ca(2+)-free form of calmodulin (apoCaM) often appears inert, modulating target molecules only upon conversion to its Ca(2+)-bound form. This schema has appeared to govern voltage-gated Ca(2+) channels, where apoCaM has been considered a dormant Ca(2+) sensor, associated with channels but awaiting the binding of Ca(2+) ions before inhibiting channel opening to provide vital feedback inhibition. Using single-molecule measurements of channels and chemical dimerization to elevate apoCaM, we find that apoCaM binding on its own markedly upregulates opening, rivaling the strongest forms of modulation. Upon Ca(2+) binding to this CaM, inhibition may simply reverse the initial upregulation. As RNA-edited and -spliced channel variants show different affinities for apoCaM, the apoCaM-dependent control mechanisms may underlie the functional diversity of these variants and explain an elongation of neuronal action potentials by apoCaM. More broadly, voltage-gated Na channels adopt this same modulatory principle. ApoCaM thus imparts potent and pervasive ion-channel regulation. PAPERCLIP:
authors.affiliation: Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, Center for Cell Dynamics, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Adams
authors.affiliation: Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, Center for Cell Dynamics, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Manu
authors.initials: M
authors.lastname: Ben-Johny
authors.affiliation: Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, Center for Cell Dynamics, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Ivy E
authors.initials: IE
authors.lastname: Dick
authors.affiliation: Department of Cell Biology and Center for Cell Dynamics, The Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, MD 21205, USA; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, Center for Cell Dynamics, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. Electronic address: dyue@jhmi.edu.
authors.forename: David T
authors.initials: DT
authors.lastname: Yue
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D006801:Humans; D051379:Mice; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism
chemical_list: C472073:CACNA1D protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002147:Calmodulin; D015222:Sodium Channels; C093712:Cacna1d protein, rat