title: Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage-Gated Calcium and Sodium Channels.
abstract: Voltage-gated Na and Ca(2+) channels represent two major ion channel families that enable myriad biological functions including the generation of action potentials and the coupling of electrical and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises a vital feedback mechanism with distinct physiological implications. Though long-sought, a shared understanding of the channel families remained elusive for two decades as the functional manifestations and the structural underpinnings of this modulation often appeared to diverge. Here, we review recent advancements in the understanding of calmodulation of Ca(2+) and Na channels that suggest a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles to approach related channelopathic diseases. An exciting era of synergistic study now looms.
authors.forename: Manu
authors.initials: M
authors.lastname: Ben-Johny
authors.forename: Ivy E
authors.initials: IE
authors.lastname: Dick
authors.forename: Lingjie
authors.initials: L
authors.lastname: Sang
authors.forename: Worawan B
authors.initials: WB
authors.lastname: Limpitikul
authors.forename: Po Wei
authors.initials: PW
authors.lastname: Kang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Niu
authors.forename: Rahul
authors.initials: R
authors.lastname: Banerjee
authors.forename: Wanjun
authors.initials: W
authors.lastname: Yang
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Babich
authors.forename: John B
authors.initials: JB
authors.lastname: Issa
authors.forename: Shin Rong
authors.initials: SR
authors.lastname: Lee
authors.forename: Ho
authors.initials: H
authors.lastname: Namkung
authors.forename: Jiangyu
authors.initials: J
authors.lastname: Li
authors.forename: Manning
authors.initials: M
authors.lastname: Zhang
authors.forename: Philemon S
authors.initials: PS
authors.lastname: Yang
authors.forename: Hojjat
authors.initials: H
authors.lastname: Bazzazi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Adams
authors.forename: Rosy
authors.initials: R
authors.lastname: Joshi-Mukherjee
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Yue
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, MD 21205, USA. manu@jhmi.edu.
authors.forename: David T
authors.initials: DT
authors.lastname: Yue
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002147:Calmodulin; D061566:Voltage-Gated Sodium Channels; D002118:Calcium