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Castillo","year":"2007","journal-title":"Eur J Neurosci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1085\/jgp.200910337","article-title":"Olfactory response termination involves Ca2+-ATPase in vertebrate olfactory receptor neuron cilia","volume":"135","author":"S Antolin","year":"2010","journal-title":"J Gen Physiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e5266","DOI":"10.1371\/journal.pone.0005266","article-title":"Limits of calcium clearance by plasma membrane calcium ATPase in olfactory cilia","volume":"4","author":"SJ Kleene","year":"2009","journal-title":"PLoS One"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e37148","DOI":"10.1371\/journal.pone.0037148","article-title":"A selective PMCA inhibitor does not prolong the electroolfactogram in mouse","volume":"7","author":"ER Griff","year":"2012","journal-title":"PLoS 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Menini","year":"1995","journal-title":"Nature"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/chemse\/25.4.473","article-title":"The cellular and molecular basis of odor adaptation","volume":"25","author":"F Zufall","year":"2000","journal-title":"Chem Senses"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1472-8206.2008.00633.x","article-title":"The Hill equation: a review of its capabilities in pharmacological modelling","volume":"22","author":"S Goutelle","year":"2008","journal-title":"Fundam Clin Pharmacol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0092-8674(81)90340-8","article-title":"Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts","volume":"24","author":"SK Basu","year":"1981","journal-title":"Cell"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1042\/bj2200665","article-title":"Monensin inhibits recycling of macrophage mannose-glycoprotein receptors and ligand delivery to lysosomes","volume":"220","author":"T Wileman","year":"1984","journal-title":"Biochem J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1083\/jcb.116.6.1343","article-title":"Evidence for the regulation of exocytic transport by protein phosphorylation","volume":"116","author":"HW Davidson","year":"1992","journal-title":"J Cell Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"32931","DOI":"10.1074\/jbc.M111.224899","article-title":"Rapid dephosphorylation of G protein-coupled receptors by protein phosphatase 1\u03b2 is required for termination of \u03b2-arrestin-dependent signaling","volume":"286","author":"F P\u00f6ll","year":"2011","journal-title":"J Biol Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0076-6879(07)38006-3","article-title":"Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of 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energy coupling between Ca2+, calmodulin, skeletal muscle myosin light chain kinase, and kinase substrates","volume":"259","author":"BB Olwin","year":"1984","journal-title":"J Biol Chem"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"7479","DOI":"10.1074\/jbc.271.13.7479","article-title":"Blocking the Ca2+-induced conformational transitions in calmodulin with disulfide bonds","volume":"271","author":"RY Tan","year":"1996","journal-title":"J Biol Chem"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"7779","DOI":"10.1021\/bi00149a006","article-title":"Circular dichroism studies on calcium binding to two series of Ca2+ binding site mutants of Drosophila melanogaster calmodulin","volume":"31","author":"JF Maune","year":"1992","journal-title":"Biochemistry"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1085\/jgp.200910296","article-title":"Activation and desensitization of the olfactory cAMP-gated transduction channel: identification of functional modules","volume":"134","author":"C Waldeck","year":"2009","journal-title":"J Gen Physiol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1085\/jgp.200308888","article-title":"The Ca-activated Cl channel and its control in rat olfactory receptor neurons","volume":"122","author":"J Reisert","year":"2003","journal-title":"J Gen Physiol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1073\/pnas.90.4.1420","article-title":"A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination","volume":"90","author":"S Schleicher","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1046\/j.1471-4159.1999.0720541.x","article-title":"Internalization of G protein-coupled receptors in single olfactory receptor neurons","volume":"72","author":"ML Rankin","year":"1999","journal-title":"J Neurochem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"14325","DOI":"10.1073\/pnas.0603942103","article-title":"Visualizing odorant receptor trafficking in living cells down to the single-molecule level","volume":"103","author":"V Jacquier","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"9902","DOI":"10.1523\/JNEUROSCI.2897-06.2006","article-title":"Beta-arrestin2-mediated internalization of mammalian odorant receptors","volume":"26","author":"A Mashukova","year":"2006","journal-title":"J Neurosci"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1074\/jbc.272.7.4606","article-title":"Phosducin, potential role in modulation of olfactory signaling","volume":"272","author":"I Boekhoff","year":"1997","journal-title":"J Biol Chem"},{"key":"ref60","first-page":"165","article-title":"Up-regulation of the cAMP\/PKA pathway inhibits proliferation, induces differentiation, and leads to apoptosis in malignant gliomas","volume":"78","author":"TC Chen","year":"1998","journal-title":"Lab Invest"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.neuron.2008.02.029","article-title":"Olfactory CNG channel desensitization by Ca2+\/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation","volume":"58","author":"Y Song","year":"2008","journal-title":"Neuron"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"18677","DOI":"10.1074\/jbc.273.30.18677","article-title":"G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization","volume":"273","author":"RJ Lefkowitz","year":"1998","journal-title":"J Biol Chem"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0006-8993(84)90012-X","article-title":"Transduction physiology of olfactory receptor cilia","volume":"310","author":"GD Adamek","year":"1984","journal-title":"Brain Res"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0005-2736(88)90315-X","article-title":"Ion transport across the frog olfactory mucosa: the action of cyclic nucleotides on the basal and odorant-stimulated states","volume":"944","author":"KC Persaud","year":"1988","journal-title":"Biochim Biophys Acta"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"ra48","DOI":"10.1126\/scisignal.2003110","article-title":"Differential Regulation by Cyclic Nucleotides of the CNGA4 and CNGB1b Subunits in Olfactory Cyclic Nucleotide-Gated Channels","volume":"5","author":"V Nache","year":"2012","journal-title":"Sci Signal"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/j.1460-9568.2010.07393.x","article-title":"Cellular and molecular Ca2+ microdomains in olfactory cilia support low signaling amplification of odor transduction","volume":"32","author":"K Castillo","year":"2010","journal-title":"Eur J Neurosci"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/S0006-3495(97)78143-8","article-title":"High-gain, low-noise amplification in olfactory transduction","volume":"73","author":"SJ Kleene","year":"1997","journal-title":"Biophys J"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00217846","article-title":"Ciliated and microvillous structures of rat olfactory and nasal respiratory epithelia. A study using ultra-rapid cryo-fixation followed by freeze-substitution or freeze-etching","volume":"235","author":"BP Menco","year":"1984","journal-title":"Cell Tissue Res"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1126\/science.1109886","article-title":"Elementary response of olfactory receptor neurons to odorants","volume":"308","author":"V Bhandawat","year":"2005","journal-title":"Science"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"18682","DOI":"10.1073\/pnas.1004571107","article-title":"Signaling by olfactory receptor neurons near threshold","volume":"107","author":"V Bhandawat","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1073\/pnas.1017983108","article-title":"Unitary response of mouse olfactory receptor neurons","volume":"108","author":"Y Ben-Chaim","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1021\/bi200115m","article-title":"Distinct binding properties distinguish LQ-type calmodulin-binding domains in cyclic nucleotide-gated channels","volume":"50","author":"N Ungerer","year":"2011","journal-title":"Biochemistry"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0026-895X(24)23185-0","article-title":"Single-channel kinetics of the rat olfactory cyclic nucleotide-gated channel expressed in Xenopus oocytes","volume":"55","author":"J Li","year":"1999","journal-title":"Mol Pharmacol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1085\/jgp.115.1.59","article-title":"Bimodal control of a Ca(2+)-activated Cl(\u2212) channel by different Ca(2+) signals","volume":"115","author":"A Kuruma","year":"2000","journal-title":"J Gen Physiol"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1042\/BC20100128","article-title":"The ciliary pocket: a once-forgotten membrane domain at the base of cilia","volume":"103","author":"R Ghossoub","year":"2011","journal-title":"Biol Cell"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1091\/mbc.E12-01-0073","article-title":"The future of ciliary and flagellar membrane research","volume":"23","author":"RA Bloodgood","year":"2012","journal-title":"Mol Biol Cell"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ceb.2012.10.011","article-title":"The ciliary pocket","volume":"25","author":"A Benmerah","year":"2013","journal-title":"Curr Opin Cell Biol"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/ncb2888","article-title":"The roles of evolutionarily conserved functional modules in cilia-related trafficking","volume":"15","author":"CH Sung","year":"2013","journal-title":"Nat Cell Biol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0022-5320(84)90092-3","article-title":"Observations on axonemes and membranes of olfactory and respiratory cilia in frogs and rats using tannic acid-supplemented fixation and photographic rotation","volume":"86","author":"MS Lidow","year":"1984","journal-title":"J Ultrastruct Res"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jemt.1070220303","article-title":"Ultrastructural studies on membrane, cytoskeletal, mucous, and protective compartments in olfaction","volume":"22","author":"B Menco","year":"1992","journal-title":"Microsc Res Tech"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1093\/chemse\/22.3.295","article-title":"Ultrastructural aspects of olfactory signaling","volume":"22","author":"BP Menco","year":"1997","journal-title":"Chem Senses"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00237805","article-title":"Qualitative and quantitative freeze-fracture studies on olfactory and nasal respiratory structures of frog, ox, rat, and dog. I. A general survey","volume":"207","author":"BP Menco","year":"1980","journal-title":"Cell Tissue Res"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/chemse\/bjm073","article-title":"Proteomic analysis of a membrane preparation from rat olfactory sensory cilia","volume":"33","author":"U Mayer","year":"2008","journal-title":"Chem Senses"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"11776","DOI":"10.1073\/pnas.0903304106","article-title":"ANO2 is the cilial calcium-activated chloride channel that may mediate olfactory amplification","volume":"106","author":"AB Stephan","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2046-2530-1-4","article-title":"Trafficking in and to the primary cilium","volume":"1","author":"YC Hsiao","year":"2012","journal-title":"Cilia"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/nn.2580","article-title":"In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons","volume":"13","author":"DC Dieterich","year":"2010","journal-title":"Nat Neurosci"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1113\/jphysiol.2002.016600","article-title":"Photolysis of caged cyclic AMP in the ciliary cytoplasm of the newt olfactory receptor cell","volume":"541","author":"H Takeuchi","year":"2002","journal-title":"J Physiol"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0959-4388(03)00097-7","article-title":"Calcium, the two-faced messenger of olfactory transduction and adaptation","volume":"13","author":"HR Matthews","year":"2003","journal-title":"Curr Opin Neurobiol"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"25699","DOI":"10.1074\/jbc.271.41.25699","article-title":"The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner","volume":"271","author":"C Yan","year":"1996","journal-title":"J Biol Chem"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/310503a0","article-title":"DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1","volume":"310","author":"HC Hemmings","year":"1984","journal-title":"Nature"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0896-6273(00)80798-9","article-title":"Beyond the dopamine receptor: the DARPP-32\/protein phosphatase-1 cascade","volume":"23","author":"P Greengard","year":"1999","journal-title":"Neuron"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0896-6273(00)80561-9","article-title":"Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals","volume":"21","author":"J Wei","year":"1998","journal-title":"Neuron"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"14557","DOI":"10.1523\/JNEUROSCI.0559-12.2012","article-title":"Phosphorylation of Adenylyl Cyclase III at Serine1076 Does Not Attenuate Olfactory Response in Mice","volume":"32","author":"KD Cygnar","year":"2012","journal-title":"J Neurosci"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.7089556","article-title":"Amplification and adaptation in regulatory and sensory systems","volume":"217","author":"DE Koshland","year":"1982","journal-title":"Science"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1016\/S0021-9258(19)34116-X","article-title":"Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells","volume":"265","author":"T Chijiwa","year":"1990","journal-title":"J Biol Chem"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0026-895X(25)15265-6","article-title":"Effects of xanthine derivatives on lipolysis and on adenosine 3\u2032,5\u2032-monophosphate phosphodiesterase activity","volume":"6","author":"JA Beavo","year":"1970","journal-title":"Mol Pharmacol"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.devcel.2006.04.002","article-title":"Dynasore, a cell-permeable inhibitor of dynamin","volume":"10","author":"E Macia","year":"2006","journal-title":"Dev Cell"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1042\/bj2560283","article-title":"Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics","volume":"256","author":"C Bialojan","year":"1988","journal-title":"Biochem J"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/oxfordjournals.jbchem.a003224","article-title":"Calcium-dependent phosphorylation of a protein in the frog olfactory cilia","volume":"132","author":"K Katanosaka","year":"2002","journal-title":"J Biochem"},{"key":"ref100","article-title":"Analyzing responses of mouse olfactory sensory neurons using the air-phase electroolfactogram recording","author":"KD Cygnar","year":"2010","journal-title":"J Vis Exp"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1093\/bioinformatics\/btl485","article-title":"COPASI\u2014a COmplex PAthway SImulator","volume":"22","author":"S Hoops","year":"2006","journal-title":"Bioinformatics"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1752-0509-6-91","article-title":"Condor-COPASI: high-throughput computing for biochemical networks","volume":"6","author":"E Kent","year":"2012","journal-title":"BMC Syst Biol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1113\/jphysiol.2002.035824","article-title":"Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k","volume":"551","author":"H Schmidt","year":"2003","journal-title":"J Physiol"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1126\/science.266.5189.1348","article-title":"Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel","volume":"266","author":"M Liu","year":"1994","journal-title":"Science"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.neuroscience.2007.11.023","article-title":"Calcium-signaling networks in olfactory receptor neurons","volume":"151","author":"D Klimmeck","year":"2008","journal-title":"Neuroscience"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BJ20070255","article-title":"Structures and metal-ion-binding properties of the Ca2+-binding helix-loop-helix EF-hand motifs","volume":"405","author":"JL Gifford","year":"2007","journal-title":"Biochem J"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0962-8924(00)01800-6","article-title":"Calmodulin: a prototypical calcium sensor","volume":"10","author":"D Chin","year":"2000","journal-title":"Trends Cell Biol"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"8050","DOI":"10.1016\/S0021-9258(18)92938-8","article-title":"Calcium binding to calmodulin and its globular domains","volume":"266","author":"S Linse","year":"1991","journal-title":"J Biol Chem"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1021\/bi00516a035","article-title":"Effects of cations on affinity of calmodulin for calcium: ordered binding of calcium ions allows the specific activation of calmodulin-stimulated enzymes","volume":"20","author":"J Haiech","year":"1981","journal-title":"Biochemistry"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"6027","DOI":"10.1016\/S0021-9258(18)38077-3","article-title":"Use of site-directed mutations in the individual Ca2(+)-binding sites of calmodulin to examine Ca2(+)-induced conformational changes","volume":"266","author":"K Beckingham","year":"1991","journal-title":"J Biol Chem"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1021\/bi9628275","article-title":"NMR studies of the E140Q mutant of the carboxy-terminal domain of calmodulin reveal global conformational exchange in the Ca2+-saturated state","volume":"36","author":"J Even\u00e4s","year":"1997","journal-title":"Biochemistry"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jmb.2006.03.066","article-title":"Structural basis for diversity of the EF-hand calcium-binding proteins","volume":"359","author":"Z Grabarek","year":"2006","journal-title":"J Mol Biol"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1006\/jmbi.1999.2770","article-title":"Backbone dynamics and energetics of a calmodulin domain mutant exchanging between closed and open conformations","volume":"289","author":"J Even\u00e4s","year":"1999","journal-title":"J Mol Biol"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1006\/jmbi.1999.3188","article-title":"Structural dynamics in the C-terminal domain of calmodulin at low calcium levels","volume":"293","author":"A Malmendal","year":"1999","journal-title":"J Mol Biol"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"13744","DOI":"10.1021\/bi9806448","article-title":"Ca2+ binding and conformational changes in a calmodulin domain","volume":"37","author":"J Even\u00e4s","year":"1998","journal-title":"Biochemistry"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1021\/bi0497852","article-title":"Ab initio study of NMR 15N chemical shift differences induced by Ca2+ binding to EF-hand proteins","volume":"43","author":"RR Biekofsky","year":"2004","journal-title":"Biochemistry"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1021\/bi7013129","article-title":"The neuronal voltage-dependent sodium channel type II IQ motif lowers the calcium affinity of the C-domain of calmodulin","volume":"47","author":"NT Theoharis","year":"2008","journal-title":"Biochemistry"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1021\/bi6025402","article-title":"Disruption of interdomain interactions via partial calcium occupancy of calmodulin","volume":"46","author":"CB Boschek","year":"2007","journal-title":"Biochemistry"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"7617","DOI":"10.1021\/bi9800449","article-title":"Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF-hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+ coordination","volume":"37","author":"RR Biekofsky","year":"1998","journal-title":"Biochemistry"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1021\/bi951934g","article-title":"Calcium-induced interactions of calmodulin domains revealed by quantitative thrombin footprinting of Arg37 and Arg106","volume":"35","author":"MA Shea","year":"1996","journal-title":"Biochemistry"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/prot.22917","article-title":"Recognition of \u03b2-calcineurin by the domains of calmodulin: thermodynamic and structural evidence for distinct roles","volume":"79","author":"SE O'Donnell","year":"2011","journal-title":"Proteins"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0969-2126(01)00575-5","article-title":"Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant","volume":"9","author":"J Even\u00e4s","year":"2001","journal-title":"Structure"},{"key":"ref123","doi-asserted-by":"crossref","first-page":"11844","DOI":"10.1021\/bi9909288","article-title":"Battle for the EF-hands: magnesium-calcium interference in calmodulin","volume":"38","author":"A Malmendal","year":"1999","journal-title":"Biochemistry"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/pro.5560050701","article-title":"Target recognition by calmodulin: dissecting the kinetics and affinity of interaction using short peptide sequences","volume":"5","author":"PM Bayley","year":"1996","journal-title":"Protein Sci"},{"key":"ref125","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1074\/jbc.272.6.3389","article-title":"Kinetic control of the dissociation pathway of calmodulin-peptide complexes","volume":"272","author":"SE Brown","year":"1997","journal-title":"J Biol Chem"},{"key":"ref126","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1074\/jbc.271.2.761","article-title":"Effects of myosin light chain kinase and peptides on Ca2+ exchange with the N- and C-terminal Ca2+ binding sites of calmodulin","volume":"271","author":"JD Johnson","year":"1996","journal-title":"J Biol Chem"},{"key":"ref127","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/nature05596","article-title":"Relating ligand binding to activation gating in CNGA2 channels","volume":"446","author":"C Biskup","year":"2007","journal-title":"Nature"},{"key":"ref128","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1113\/jphysiol.2005.092304","article-title":"Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative","volume":"569","author":"V Nache","year":"2005","journal-title":"J Physiol"},{"key":"ref129","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1529\/biophysj.108.129718","article-title":"Thermodynamics of activation gating in olfactory-type cyclic nucleotide-gated (CNGA2) channels","volume":"95","author":"V Nache","year":"2008","journal-title":"Biophys J"},{"key":"ref130","doi-asserted-by":"crossref","first-page":"9017","DOI":"10.1074\/jbc.R800075200","article-title":"Cyclic nucleotide-regulated cation channels","volume":"284","author":"M Biel","year":"2009","journal-title":"J Biol Chem"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1152\/physrev.00008.2002","article-title":"Cyclic nucleotide-gated ion channels","volume":"82","author":"UB Kaupp","year":"2002","journal-title":"Physiol Rev"},{"key":"ref132","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1126\/science.1063415","article-title":"Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits","volume":"294","author":"J Bradley","year":"2001","journal-title":"Science"},{"key":"ref133","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4161\/chan.4366","article-title":"Na+\/Ca2+-K+ exchangers (NCKX): functional properties and physiological roles","volume":"1","author":"HF Altimimi","year":"2007","journal-title":"Channels (Austin)"},{"key":"ref134","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1749-6632.1991.tb17285.x","article-title":"The stoichiometry of Na-Ca+K exchange in rod outer segments isolated from bovine retinas","volume":"639","author":"PP Schnetkamp","year":"1991","journal-title":"Ann N Y Acad Sci"},{"key":"ref135","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1085\/jgp.201110764","article-title":"The voltage dependence of the TMEM16B\/anoctamin2 calcium-activated chloride channel is modified by mutations in the first putative intracellular loop","volume":"139","author":"V Cenedese","year":"2012","journal-title":"J Gen Physiol"},{"key":"ref136","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nn.2821","article-title":"Ca2+-activated Cl\u2212 currents are dispensable for olfaction","volume":"14","author":"GM Billig","year":"2011","journal-title":"Nat Neurosci"},{"key":"ref137","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1085\/jgp.100.1.45","article-title":"Properties of cyclic nucleotide-gated channels mediating olfactory transduction. Activation, selectivity, and blockage","volume":"100","author":"S Frings","year":"1992","journal-title":"J Gen Physiol"},{"key":"ref138","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1016\/S0006-3495(03)70064-2","article-title":"Contribution of cyclic-nucleotide-gated channels to the resting conductance of olfactory receptor neurons","volume":"84","author":"RY Pun","year":"2003","journal-title":"Biophys J"},{"key":"ref139","unstructured":"Ottoson D (1955) Analysis of the electrical activity of the olfactory epithelium. Acta Physiol Scand Suppl 35: 1\u201383."},{"key":"ref140","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1093\/chemse\/bjg063","article-title":"Whole-cell recordings and photolysis of caged compounds in olfactory sensory neurons isolated from the mouse","volume":"28","author":"L Lagostena","year":"2003","journal-title":"Chem Senses"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0167-4889(96)00030-4","article-title":"Phosphatase 2A regulates the responsiveness of olfactory cilia","volume":"1312","author":"C Kroner","year":"1996","journal-title":"Biochim Biophys Acta"},{"key":"ref142","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1137\/070692017","article-title":"Fast monte carlo simulation methods for biological reaction-diffusion systems in solution and on surfaces","volume":"30","author":"RA Kerr","year":"2008","journal-title":"SIAM J Sci Comput"},{"key":"ref143","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1126\/science.1108239","article-title":"Evidence for ectopic neurotransmission at a neuronal synapse","volume":"309","author":"JS Coggan","year":"2005","journal-title":"Science"},{"key":"ref144","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/chemse\/bjp008","article-title":"Role of plasma membrane calcium ATPases in calcium clearance from olfactory sensory neurons","volume":"34","author":"SP Saidu","year":"2009","journal-title":"Chem Senses"},{"key":"ref145","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1085\/jgp.102.5.907","article-title":"Odorant-regulated Ca2+ gradients in rat olfactory neurons","volume":"102","author":"D Restrepo","year":"1993","journal-title":"J Gen Physiol"},{"key":"ref146","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0167-4889(95)00105-2","article-title":"Calcium signals in olfactory neurons","volume":"1269","author":"E Tareilus","year":"1995","journal-title":"Biochim Biophys Acta"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0105531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T09:10:37Z","timestamp":1746349837000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0105531"}},"subtitle":[],"editor":[{"given":"Manabu","family":"Sakakibara","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2014,8,21]]},"references-count":146,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2014,8,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0105531","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,21]]}}}