XB-ART-56457
Neuron
2019 Mar 20;1016:1134-1149.e3. doi: 10.1016/j.neuron.2019.01.011.
Show Gene links
Show Anatomy links
A Selectivity Filter Gate Controls Voltage-Gated Calcium Channel Calcium-Dependent Inactivation.
Abderemane-Ali F
,
Findeisen F
,
Rossen ND
,
Minor DL
.
???displayArticle.abstract???
Calcium-dependent inactivation (CDI) is a fundamental autoregulatory mechanism in CaV1 and CaV2 voltage-gated calcium channels. Although CDI initiates with the cytoplasmic calcium sensor, how this event causes CDI has been elusive. Here, we show that a conserved selectivity filter (SF) domain II (DII) aspartate is essential for CDI. Mutation of this residue essentially eliminates CDI and leaves key channel biophysical characteristics untouched. DII mutants regain CDI by placing an aspartate at the analogous SF site in DIII or DIV, but not DI, indicating that CaV SF asymmetry is key to CDI. Together, our data establish that the CaV SF is the CDI endpoint. Discovery of this SF CDI gate recasts the CaV inactivation paradigm, placing it squarely in the framework of voltage-gated ion channel (VGIC) superfamily members in which SF-based gating is important. This commonality suggests that SF inactivation is an ancient process arising from the shared VGIC pore architecture.
???displayArticle.pubmedLink??? 30733149
???displayArticle.pmcLink??? PMC8878153
???displayArticle.link??? Neuron
???displayArticle.grants??? [+]
R01 HL080050 NHLBI NIH HHS
Species referenced: Xenopus laevis
Genes referenced: cav1 cav2
References [+] :
Adams,
Apocalmodulin itself promotes ion channel opening and Ca(2+) regulation.
2014, Pubmed
Adams, Apocalmodulin itself promotes ion channel opening and Ca(2+) regulation. 2014, Pubmed
Ader, Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity. 2009, Pubmed
Almagor, The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis. 2012, Pubmed , Xenbase
Alseikhan, Engineered calmodulins reveal the unexpected eminence of Ca2+ channel inactivation in controlling heart excitation. 2002, Pubmed
Arrigoni, Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation. 2016, Pubmed
Autzen, Structure of the human TRPM4 ion channel in a lipid nanodisc. 2018, Pubmed
Babich, Role of extracellular Ca2+ in gating of CaV1.2 channels. 2005, Pubmed
Babich, Ca2+-dependent inactivation of CaV1.2 channels prevents Gd3+ block: does Ca2+ block the pore of inactivated channels? 2007, Pubmed
Bagriantsev, Multiple modalities converge on a common gate to control K2P channel function. 2011, Pubmed
Barrett, The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. 2008, Pubmed
Bartels, Alternative Splicing at N Terminus and Domain I Modulates CaV1.2 Inactivation and Surface Expression. 2018, Pubmed
Ben Johny, Dynamic switching of calmodulin interactions underlies Ca2+ regulation of CaV1.3 channels. 2013, Pubmed
Ben-Johny, Calmodulin regulation (calmodulation) of voltage-gated calcium channels. 2014, Pubmed
Benmocha Guggenheimer, Interactions between N and C termini of α1C subunit regulate inactivation of CaV1.2 L-type Ca(2+) channel. 2016, Pubmed , Xenbase
Bock, Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels. 2011, Pubmed
Campiglio, The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels. 2015, Pubmed
Cao, TRPV1 structures in distinct conformations reveal activation mechanisms. 2013, Pubmed
Catterall, Voltage-gated calcium channels. 2011, Pubmed
Catterall, The chemical basis for electrical signaling. 2017, Pubmed
Cens, Voltage and calcium use the same molecular determinants to inactivate calcium channels. 1999, Pubmed
Cens, Voltage- and calcium-dependent inactivation in high voltage-gated Ca(2+) channels. 2006, Pubmed , Xenbase
Chen, Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels. 2004, Pubmed
Cheng, Structural modeling of calcium binding in the selectivity filter of the L-type calcium channel. 2010, Pubmed
Christel, Ca2+-dependent modulation of voltage-gated Ca2+ channels. 2012, Pubmed
Clapham, Calcium signaling. 2007, Pubmed
Cohen, A novel mechanism for human K2P2.1 channel gating. Facilitation of C-type gating by protonation of extracellular histidine residues. 2008, Pubmed , Xenbase
Cuello, Structural mechanism of C-type inactivation in K(+) channels. 2010, Pubmed
Cuello, The gating cycle of a K+ channel at atomic resolution. 2017, Pubmed
De Waard, Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes. 1995, Pubmed , Xenbase
DeMaria, Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels. 2001, Pubmed
Dick, A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels. 2008, Pubmed
Dick, Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation. 2016, Pubmed
Doering, Cav1.4 encodes a calcium channel with low open probability and unitary conductance. 2005, Pubmed
Dolphin, Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology. 2016, Pubmed
Dunlap, Calcium channels are models of self-control. 2007, Pubmed
Ellinor, Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions. 1995, Pubmed , Xenbase
Fallon, Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel. 2005, Pubmed
Fallon, Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins. 2009, Pubmed
Findeisen, Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation. 2009, Pubmed , Xenbase
Halling, Regulation of voltage-gated Ca2+ channels by calmodulin. 2006, Pubmed
Hamill, Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. 1981, Pubmed
Hess, Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. , Pubmed
Huang, RNA editing of the IQ domain in Ca(v)1.3 channels modulates their Ca²⁺-dependent inactivation. 2012, Pubmed
Huang, C-terminal alternative splicing of CaV1.3 channels distinctively modulates their dihydropyridine sensitivity. 2013, Pubmed
Imai, Structural basis underlying the dual gate properties of KcsA. 2010, Pubmed
Ivanina, Modulation of L-type Ca2+ channels by gbeta gamma and calmodulin via interactions with N and C termini of alpha 1C. 2000, Pubmed
Kim, Structural determinants of ion selectivity in brain calcium channel. 1993, Pubmed , Xenbase
Kim, Identification of the components controlling inactivation of voltage-gated Ca2+ channels. 2004, Pubmed , Xenbase
Kim, Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation. 2008, Pubmed
Koishi, A superfamily of voltage-gated sodium channels in bacteria. 2004, Pubmed
Lee, Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. 1999, Pubmed
Lee, Molecular determinants of Ca(2+)/calmodulin-dependent regulation of Ca(v)2.1 channels. 2003, Pubmed
Liang, Unified mechanisms of Ca2+ regulation across the Ca2+ channel family. 2003, Pubmed
Limpitikul, Calmodulin mutations associated with long QT syndrome prevent inactivation of cardiac L-type Ca(2+) currents and promote proarrhythmic behavior in ventricular myocytes. 2014, Pubmed
Limpitikul, An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation. 2016, Pubmed
Limpitikul, A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome. 2017, Pubmed
Liu, Dynamic rearrangement of the outer mouth of a K+ channel during gating. 1996, Pubmed
Lolicato, K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. 2017, Pubmed , Xenbase
López-Barneo, Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels. 1993, Pubmed , Xenbase
Mahajan, Modifying L-type calcium current kinetics: consequences for cardiac excitation and arrhythmia dynamics. 2008, Pubmed
Mikala, Differential contribution by conserved glutamate residues to an ion-selectivity site in the L-type Ca2+ channel pore. 1993, Pubmed
Minor, Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation. 2010, Pubmed
Mori, Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+. 2008, Pubmed
Morotti, Theoretical study of L-type Ca(2+) current inactivation kinetics during action potential repolarization and early afterdepolarizations. 2012, Pubmed
Nanou, Calcium Channels, Synaptic Plasticity, and Neuropsychiatric Disease. 2018, Pubmed
Noceti, Effect of bay K 8644 (-) and the beta2a subunit on Ca2+-dependent inactivation in alpha1C Ca2+ channels. 1998, Pubmed , Xenbase
Ogielska, Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation. 1999, Pubmed , Xenbase
Olcese, The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation. 1994, Pubmed , Xenbase
Opatowsky, Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. 2004, Pubmed
Panyi, Cross talk between activation and slow inactivation gates of Shaker potassium channels. 2006, Pubmed
Parent, Glutamate substitution in repeat IV alters divalent and monovalent cation permeation in the heart Ca2+ channel. 1995, Pubmed , Xenbase
Pavlov, The pore, not cytoplasmic domains, underlies inactivation in a prokaryotic sodium channel. 2005, Pubmed
Payandeh, Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. 2015, Pubmed
Payandeh, The crystal structure of a voltage-gated sodium channel. 2011, Pubmed
Payandeh, Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. 2012, Pubmed
Peters, Allosteric coupling of the inner activation gate to the outer pore of a potassium channel. 2013, Pubmed
Peterson, Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels. 1999, Pubmed
Piechotta, The pore structure and gating mechanism of K2P channels. 2011, Pubmed
Raybaud, The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+ channels. 2006, Pubmed , Xenbase
Ren, A prokaryotic voltage-gated sodium channel. 2001, Pubmed
Schewe, A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels. 2016, Pubmed
Shaya, Voltage-gated sodium channel (NaV) protein dissection creates a set of functional pore-only proteins. 2011, Pubmed
Shaya, Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels. 2014, Pubmed
Shen, Alternative splicing of the Ca(v)1.3 channel IQ domain, a molecular switch for Ca2+-dependent inactivation within auditory hair cells. 2006, Pubmed
Simms, Neuronal voltage-gated calcium channels: structure, function, and dysfunction. 2014, Pubmed
Singh, C-terminal modulator controls Ca2+-dependent gating of Ca(v)1.4 L-type Ca2+ channels. 2006, Pubmed
Singh, Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain. 2008, Pubmed
Splawski, Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. 2004, Pubmed , Xenbase
Splawski, Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. 2005, Pubmed , Xenbase
Stea, Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels. 1994, Pubmed , Xenbase
Steinberg, Conformational dynamics in TRPV1 channels reported by an encoded coumarin amino acid. 2017, Pubmed
Stotz, Functional roles of cytoplasmic loops and pore lining transmembrane helices in the voltage-dependent inactivation of HVA calcium channels. 2004, Pubmed
Tadross, Systematic mapping of the state dependence of voltage- and Ca2+-dependent inactivation using simple open-channel measurements. 2010, Pubmed
Tadross, Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel. 2008, Pubmed
Tadross, Molecular endpoints of Ca2+/calmodulin- and voltage-dependent inactivation of Ca(v)1.3 channels. 2010, Pubmed
Tadross, Ca2+ channel nanodomains boost local Ca2+ amplitude. 2013, Pubmed
Tan, Functional characterization of alternative splicing in the C terminus of L-type CaV1.3 channels. 2011, Pubmed
Van Petegem, Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain. 2004, Pubmed
Van Petegem, Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex. 2005, Pubmed
Wu, Structure of the voltage-gated calcium channel Cav1.1 complex. 2015, Pubmed
Wu, Structure of the voltage-gated calcium channel Ca(v)1.1 at 3.6 Å resolution. 2016, Pubmed
Xu, Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. 2001, Pubmed , Xenbase
Yang, Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels. 1993, Pubmed , Xenbase
Yang, CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum. 2015, Pubmed
Yu, Overview of molecular relationships in the voltage-gated ion channel superfamily. 2005, Pubmed
Yue, The cation selectivity filter of the bacterial sodium channel, NaChBac. 2002, Pubmed
Zamponi, The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. 2015, Pubmed
Zong, Molecular determinants of calcium-dependent inactivation in cardiac L-type calcium channels. 1994, Pubmed
Zühlke, Calmodulin supports both inactivation and facilitation of L-type calcium channels. 1999, Pubmed , Xenbase