Genomes and Genes
Geoffrey S Pitt
Affiliation: Columbia University
- KCNQ1 assembly and function is blocked by long-QT syndrome mutations that disrupt interaction with calmodulinSmita Ghosh
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Circ Res 98:1048-54. 2006..These findings offer a new mechanism for LQTS defects and provide a basis for understanding novel ways that intracellular Ca2+ and CaM regulate ion channels...
- Molecular basis of calmodulin tethering and Ca2+-dependent inactivation of L-type Ca2+ channelsG S Pitt
Department of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305, USA
J Biol Chem 276:30794-802. 2001..When the C-terminal lobe of CaM binds to the nearby CaM effector sequence (IQ motif), the braking effect is relieved, and CDI is accelerated...
- Calmodulin and CaMKII as molecular switches for cardiac ion channelsGeoffrey S Pitt
Department of Medicine, Division of Cardiology, College of Physicians and Surgeons of Columbia University, 630 W 168th St, PH 7W 318, New York, NY 10032, USA
Cardiovasc Res 73:641-7. 2007..This review highlights various mechanisms by which CaM and CaMKII regulate cardiovascular ion channel activity and presents a novel model for CaMKII regulation of Ca(V)1.2 Ca(2+) channel function...
- Crystal structure of the ternary complex of a NaV C-terminal domain, a fibroblast growth factor homologous factor, and calmodulinChaojian Wang
Division of Cardiology, Department of Medicine, Duke University Medical Center, 2 Genome Ct, Durham, NC 27710, USA
Structure 20:1167-76. 2012..Furthermore, we identify a critical interaction that contributes to the specificity of individual Na(V) CTD isoforms for distinctive FHFs...
- CaMKII tethers to L-type Ca2+ channels, establishing a local and dedicated integrator of Ca2+ signals for facilitationAndy Hudmon
Department of Neurobiology, Stanford University, Stanford, CA 94305, USA
J Cell Biol 171:537-47. 2005..These findings clarify the molecular basis of CDF and demonstrate a novel enzymatic mechanism by which ion channel gating can be modulated by activity...
- Solution structure of the NaV1.2 C-terminal EF-hand domainVesselin Z Miloushev
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032 3702, USA
J Biol Chem 284:6446-54. 2009..Clinically significant mutations identified in the C-terminal region of NaV1 sodium channels cluster in the helix I-IV interface and the helix II-III interhelical segment or in helices III and IV of the NaV1.2 (1777-1882) structure...
- The auxiliary subunit KChIP2 is an essential regulator of homeostatic excitabilityHong Gang Wang
Division of Cardiology, Department of Medicine, Duke University, Medical Center, Durham, NC 27710, USA
J Biol Chem 288:13258-68. 2013..The necessity for, or redundancy of, distinctive KChIP proteins is not known...
- Rem2-targeted shRNAs reduce frequency of miniature excitatory postsynaptic currents without altering voltage-gated Ca²⁺ currentsHong Gang Wang
Division of Cardiology, Department of Medicine, and the Ion Channel Research Unit, Duke University Medical Center, Durham, North Carolina, United States of America
PLoS ONE 6:e25741. 2011..In addition, our results reveal a surprising lack of contribution of VGCCs to synaptogenesis during early development in cultured hippocampal neurons...
- Calmodulin mediates Ca2+ sensitivity of sodium channelsJames Kim
Department of Pharmacology, Division of Cardiology, Columbia University, New York, New York 10032, USA
J Biol Chem 279:45004-12. 2004..Together, these data offer new biochemical evidence for Ca2+/CaM modulation of Na+ channel function...
- Ca2+/CaM controls Ca2+-dependent inactivation of NMDA receptors by dimerizing the NR1 C terminiChaojian Wang
Department of Medicine, Duke University, Durham, North Carolina 27710, USA
J Neurosci 28:1865-70. 2008..We propose a new model for CDI in which the noncanonical Ca2+/CaM-dependent dimerization of the two NR1 subunits inactivates the channel by propagating a conformational change from the short NR1 CT to the nearby channel pore...
- Identification of novel interaction sites that determine specificity between fibroblast growth factor homologous factors and voltage-gated sodium channelsChaojian Wang
Ion Channel Research Unit, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 286:24253-63. 2011..Together, these results give new insights into details of the interactions between FHFs and Na(V)1.x CTs, and the consequent regulation of Na(+) channels...
- Accessory subunit KChIP2 modulates the cardiac L-type calcium currentMorten B Thomsen
Department of Medicine, Duke University Medical Center, Box 103030 Medical Center, Durham, NC 27710, USA
Circ Res 104:1382-9. 2009..2, resulting in increased I(Ca,L). In the context of recent reports that KChIP2 modulates multiple K(V) and Na(V) currents, these results suggest that KChIP2 is a multimodal regulator of cardiac ionic currents...
- Ca2+/calmodulin regulates trafficking of Ca(V)1.2 Ca2+ channels in cultured hippocampal neuronsHong Gang Wang
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
J Neurosci 27:9086-93. 2007..Furthermore, this Ca2+/CaM-accelerated trafficking was activity dependent. Thus, CaM imparts Ca2+-dependent regulation not only to mature Ca(V)1.2 channels at the cell surface but also to steps during channel biosynthesis...
- Dose-dependent and isoform-specific modulation of Ca2+ channels by RGK GTPasesLillian Seu
Department of Pharmacology, Division of Cardiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
J Gen Physiol 128:605-13. 2006..Together, these results offer new insights into the molecular mechanism of RGK-mediated Ca(2+) channel current modulation...
- Essential Ca(V)beta modulatory properties are AID-independentJanet M Maltez
Department of Pharmacology, Columbia University, New York, New York 10032, USA
Nat Struct Mol Biol 12:372-7. 2005....
- Remodeled cardiac calcium channelsGeoffrey S Pitt
Department of Medicine, Columbia University, New York, NY, USA
J Mol Cell Cardiol 41:373-88. 2006..In addition, it will review the recent advances made in our understanding of the function of the various molecular building blocks that contribute to the proper functioning of the cardiac calcium channel...
- The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fractionAlbert Y Sun
Division of Cardiovascular Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA
Circ Cardiovasc Genet 4:163-8. 2011..We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction...
- Identification of the components controlling inactivation of voltage-gated Ca2+ channelsJames Kim
Department of Pharmacology, College of Physicians and Surgeons, of Columbia University, 630 West 168th Street, PH 7W 318, New York, NY 10032 USA
Neuron 41:745-54. 2004....
- The real estate of cardiac signaling: location, location, locationMeena S George
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Proc Natl Acad Sci U S A 103:7535-6. 2006
- Genetics of cardiac repolarizationSvati H Shah
Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC, USA
Nat Genet 41:388-9. 2009..Two genome-wide association studies (GWAS) of variation in the QT interval in population-based cohorts now report association with variants in a subset of ion channel genes and other new associations...
- FGF14 regulates presynaptic Ca2+ channels and synaptic transmissionHaidun Yan
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Cell Rep 4:66-75. 2013..Thus, FHFs are multimodal, regulating several discrete neuronal signaling events. SCA27 most likely results at least in part from dysregulation of Ca2+ channel function...
- Aldosterone, ion channels, and sudden death: another piece of the circle?Geoffrey S Pitt
Am J Physiol Heart Circ Physiol 290:H2176-7. 2006