Photo of David E. Clapham,  MD, PhD

David E. Clapham, MD, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2680
Fax: (617) 731-0787


dclapham@enders.tch.harvard.edu

David E. Clapham, MD, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Aldo R. Castaneda Professor of Cardiovascular, Neurobiology, Harvard Medical School
  • Aldo R. Castaneda Professor of Cardiovascular, Pediatrics, Harvard Medical School
  • Aldo R. Castaneda Professor of Cardiovascular Research, Howard Hughes Medical Institute, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Clapham laboratory discovers and elucidates the structure and function of ion channels, as well as their role in overall biology of the organism. Recently we identified ion channels in primary cilia that are linked to Hedgehog signaling, a target of cancer therapies. We employ patch clamp electrophysiology, advanced imaging, biochemistry, and genetic manipulation to identify the genes that encode ion channels and their associated proteins. We are currently investigating the following channels and transporters:

TRP channels (TRPC1,4,5; TRPV3, 4; TRPM6, TRPM7)

Voltage-gated proton channels (Hv1)

Mitochondrial channels (MCU and its subunits)

Mitochondrial transporters (Letm1)

Cilia channels (PKD and PKDL)

Osmosensitive chloride channels

Sperm-specific ion channels (CatSper, Slo3)

 

Publications

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  • Cai X, Wang X, Clapham DE. Early Evolution of the Eukaryotic Ca2+ Signaling Machinery: Conservation of the CatSper Channel Complex. Mol. Biol. Evol. 2014; 31:2735-40. PubMed
  • Bagnéris C, DeCaen PG, Naylor CE, Pryde DC, Nobeli I, Clapham DE, Wallace BA. Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism. Proc Natl Acad Sci U S A 2014; 111:8428-33. PubMed
  • Krapivinsky G, Krapivinsky L, Manasian Y, Clapham DE. The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell 2014; 157:1061-72. PubMed
  • Chung JJ, Shim SH, Everley RA, Gygi SP, Zhuang X, Clapham DE. Structurally distinct Ca(2+) signaling domains of sperm flagella orchestrate tyrosine phosphorylation and motility. Cell 2014; 157:808-22. PubMed
  • Py BF, Jin M, Desai BN, Penumaka A, Zhu H, Kober M, Dietrich A, Lipinski MM, Henry T, Clapham DE, Yuan J. Caspase-11 Controls Interleukin-1硫 Release through Degradation of TRPC1. Cell Rep 2014; 6:1122-8. PubMed
  • Kahle KT, Khanna A, Clapham DE, Woolf CJ. Therapeutic Restoration of Spinal Inhibition via Druggable Enhancement of Potassium-Chloride Cotransporter KCC2-Mediated Chloride Extrusion in Peripheral Neuropathic Pain. JAMA Neurol 2014. PubMed
  • Riccio A, Li Y, Tsvetkov E, Gapon S, Yao GL, Smith KS, Engin E, Rudolph U, Bolshakov VY, Clapham DE. Decreased anxiety-like behavior and G留q/11-dependent responses in the amygdala of mice lacking TRPC4 channels. J Neurosci 2014; 34:3653-67. PubMed
  • Sancak Y, Markhard AL, Kitami T, Kovács-Bogdán E, Kamer KJ, Udeshi ND, Carr SA, Chaudhuri D, Clapham DE, Li AA, Calvo SE, Goldberger O, Mootha VK. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science 2013; 342:1379-82. PubMed
  • DeCaen PG, Delling M, Vien TN, Clapham DE. Direct recording and molecular identification of the calcium channel of primary cilia. Nature 2013; 504:315-8. PubMed
  • Carvacho I, Lee HC, Fissore RA, Clapham DE. TRPV3 channels mediate strontium-induced mouse-egg activation. Cell Rep 2013; 5:1375-86. PubMed
  • Delling M, DeCaen PG, Doerner JF, Febvay S, Clapham DE. Primary cilia are specialized calcium signalling organelles. Nature 2013; 504:311-4. PubMed
  • Zeng XH, Navarro B, Xia XM, Clapham DE, Lingle CJ. Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa. J Gen Physiol 2013; 142:305-13. PubMed
  • Sah R, Mesirca P, Van den Boogert M, Rosen J, Mably J, Mangoni ME, Clapham DE. Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. Proc Natl Acad Sci U S A 2013; 110:E3037-46. PubMed
  • Mesirca P, Marger L, Toyoda F, Rizzetto R, Audoubert M, Dubel S, Torrente AG, Difrancesco ML, Muller JC, Leoni AL, Couette B, Nargeot J, Clapham DE, Wickman K, Mangoni ME. The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation. J Gen Physiol 2013; 142:113-26. PubMed
  • Sah R, Mesirca P, Mason X, Gibson W, Bates-Withers C, Van den Boogert M, Chaudhuri D, Pu WT, Mangoni ME, Clapham DE. Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization. Circulation 2013; 128:101-14. PubMed
  • Jiang D, Zhao L, Clish CB, Clapham DE. Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome. Proc Natl Acad Sci U S A 2013; 110:E2249-54. PubMed
  • Miki K, Clapham DE. Rheotaxis guides Mammalian sperm. Curr Biol 2013; 23:443-52. PubMed
  • Cang C, Zhou Y, Navarro B, Seo YJ, Aranda K, Shi L, Battaglia-Hsu S, Nissim I, Clapham DE, Ren D. mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state. Cell 2013; 152:778-90. PubMed
  • Chaudhuri D, Sancak Y, Mootha VK, Clapham DE. MCU encodes the pore conducting mitochondrial calcium currents. Elife 2013; 2:e00704. PubMed
  • Wang X, Zhang X, Dong XP, Samie M, Li X, Cheng X, Goschka A, Shen D, Zhou Y, Harlow J, Zhu MX, Clapham DE, Ren D, Xu H. TPC Proteins Are Phosphoinositide- Activated Sodium-Selective Ion Channels in Endosomes and Lysosomes. Cell 2012; 151:372-83. PubMed
  • Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani RJ, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE, Spiegelman BM. TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis. Cell 2012; 151:96-110. PubMed
  • Desai BN, Krapivinsky G, Navarro B, Krapivinsky L, Carter BC, Febvay S, Delling M, Penumaka A, Ramsey IS, Manasian Y, Clapham DE. Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis. Dev Cell 2012; 22:1149-62. PubMed
  • Zhang X, Ren W, DeCaen P, Yan C, Tao X, Tang L, Wang J, Hasegawa K, Kumasaka T, He J, Wang J, Clapham DE, Yan N. Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. Nature 2012; 486:130-4. PubMed
  • Kaczmarek JS, Riccio A, Clapham DE. Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse. Proc Natl Acad Sci U S A 2012; 109:7888-92. PubMed
  • Jin J, Wu LJ, Jun J, Cheng X, Xu H, Andrews NC, Clapham DE. The channel kinase, TRPM7, is required for early embryonic development. Proc Natl Acad Sci U S A 2012; 109:E225-33. PubMed
  • Wu LJ, Wu G, Akhavan Sharif MR, Baker A, Jia Y, Fahey FH, Luo HR, Feener EP, Clapham DE. The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. Nat Neurosci 2012; 15:565-73. PubMed
  • Stotz SC, Clapham DE. Anion-sensitive fluorophore identifies the Drosophila swell-activated chloride channel in a genome-wide RNA interference screen. PLoS ONE 2012; 7:e46865. PubMed
  • Doerner JF, Febvay S, Clapham DE. Controlled delivery of bioactive molecules into live cells using the bacterial mechanosensitive channel MscL. Nat Commun 2012; 3:990. PubMed
  • Lishko PV, Kirichok Y, Ren D, Navarro B, Chung JJ, Clapham DE. The control of male fertility by spermatozoan ion channels. Annu Rev Physiol 2012; 74:453-75. PubMed
  • Clapham DE, Miller C. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. Proc Natl Acad Sci U S A 2011; 108:19492-7. PubMed
  • Krapivinsky G, Krapivinsky L, Stotz SC, Manasian Y, Clapham DE. POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. Proc Natl Acad Sci U S A 2011; 108:19234-9. PubMed
  • Zimmermann K, Lennerz JK, Hein A, Link AS, Kaczmarek JS, Delling M, Uysal S, Pfeifer JD, Riccio A, Clapham DE. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proc Natl Acad Sci U S A 2011; 108:18114-9. PubMed
  • Cai X, Clapham DE. Ancestral Ca2+ Signaling Machinery in Early Animal and Fungal Evolution. Mol. Biol. Evol. 2011. PubMed
  • Navarro B, Miki K, Clapham DE. ATP-activated P2X2 current in mouse spermatozoa. Proc Natl Acad Sci U S A 2011; 108:14342-7. PubMed
  • Chung JJ, Navarro B, Krapivinsky G, Krapivinsky L, Clapham DE. A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa. Nat Commun 2011; 2:153. PubMed
  • Bates-Withers C, Sah R, Clapham DE. TRPM7, the Mg(2+) Inhibited Channel and Kinase. Adv Exp Med Biol 2011; 704:173-83. PubMed
  • Wu LJ, Sweet TB, Clapham DE. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol. Rev. 2010; 62:381-404. PubMed
  • Ramsey IS, Mokrab Y, Carvacho I, Sands ZA, Sansom MS, Clapham DE. An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1. Nat Struct Mol Biol 2010; 17:869-75. PubMed
  • Febvay S, Marini DM, Belcher AM, Clapham DE. Targeted cytosolic delivery of cell-impermeable compounds by nanoparticle-mediated, light-triggered endosome disruption. Nano Lett 2010; 10:2211-9. PubMed
  • Cheng X, Jin J, Hu L, Shen D, Dong XP, Samie MA, Knoff J, Eisinger B, Liu ML, Huang SM, Caterina MJ, Dempsey P, Michael LE, Dlugosz AA, Andrews NC, Clapham DE, Xu H. TRP channel regulates EGFR signaling in hair morphogenesis and skin barrier formation. Cell 2010; 141:331-43. PubMed
  • Jiang D, Zhao L, Clapham DE. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science 2009; 326:144-7. PubMed
  • Zhou H, Clapham DE. Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development. Proc Natl Acad Sci U S A 2009; 106:15750-5. PubMed
  • Riccio A,Li Y,Moon J,Kim KS,Smith KS,Rudolph U,Gapon S,Yao GL,Tsvetkov E,Rodig SJ,Van't Veer A,Meloni EG,Carlezon WA Jr,Bolshakov VY,Clapham DE. Essential role for TRPC5 in amygdala function and fear-related behavior. Cell 2009; 137:761-72. PubMed
  • Ramsey IS,Ruchti E,Kaczmarek JS,Clapham DE. Hv1 proton channels are required for high-level NADPH oxidase-dependent superoxide production during the phagocyte respiratory burst. Proc Natl Acad Sci U S A 2009; 106:7642-7. PubMed
  • Blair NT,Kaczmarek JS,Clapham DE. Intracellular calcium strongly potentiates agonist-activated TRPC5 channels. J Gen Physiol 2009; 133:525-46. PubMed
  • Clapham DE. A STIMulus Package puts orai calcium channels to work. Cell 2009; 136:814-6. PubMed
  • Oancea E,Vriens J,Brauchi S,Jun J,Splawski I,Clapham DE. TRPM1 forms ion channels associated with melanin content in melanocytes. Sci Signal 2009; 2:ra21. PubMed
  • Zimmermann K,Hein A,Hager U,Kaczmarek JS,Turnquist BP,Clapham DE,Reeh PW. Phenotyping sensory nerve endings in vitro in the mouse. Nat Protoc 2009; 4:174-96. PubMed
  • Jin J,Desai BN,Navarro B,Donovan A,Andrews NC,Clapham DE. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis. Science 2008; 322:756-60. PubMed
  • Brauchi S,Krapivinsky G,Krapivinsky L,Clapham DE. TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane. Proc Natl Acad Sci U S A 2008; 105:8304-8. PubMed
  • Rama S, Krapivinsky G, Clapham DE, Medina I. The MUPP1-SynGAPalpha protein complex does not mediate activity-induced LTP. Mol Cell Neurosci 2008; 38:183-8. PubMed
  • Musset B, Cherny VV, Morgan D, Okamura Y, Ramsey IS, Clapham DE, Decoursey TE. Detailed comparison of expressed and native voltage-gated proton channel currents. J Physiol 2008; 586:2477-86. PubMed
  • Stotz SC, Vriens J, Martyn D, Clardy J, Clapham DE. Citral sensing by TRANSient receptor potential channels in dorsal root ganglion neurons. PLoS ONE 2008; 3:e2082. PubMed
  • Cai X,Clapham DE. Evolutionary genomics reveals lineage-specific gene loss and rapid evolution of a sperm-specific ion channel complex: CatSpers and CatSperbeta. PLoS ONE 2008; 3:e3569. PubMed
  • Clapham DE. Calcium signaling. Cell 2007; 131:1047-58. PubMed
  • Fujinami S, Sato T, Trimmer JS, Spiller BW, Clapham DE, Krulwich TA, Kawagishi I, Ito M. The voltage-gated Na+ channel NaVBP co-localizes with methyl-accepting chemotaxis protein at cell poles of alkaliphilic Bacillus pseudofirmus OF4. Microbiology 2007; 153:4027-38. PubMed
  • Xu H, Delling M, Li L, Dong X, Clapham DE. Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice. Proc Natl Acad Sci U S A 2007; 104:18321-6. PubMed
  • Liu J, Xia J, Cho KH, Clapham DE, Ren D. CatSperbeta, a novel transmembrane protein in the CatSper channel complex. J Biol Chem 2007; 282:18945-52. PubMed
  • Navarro B, Kirichok Y, Clapham DE. KSper, a pH-sensitive K+ current that controls sperm membrane potential. Proc Natl Acad Sci U S A 2007; 104:7688-92. PubMed
  • Clapham DE. SnapShot: mammalian TRP channels. Cell 2007; 129:220. PubMed
  • Qi H, Moran MM, Navarro B, Chong JA, Krapivinsky G, Krapivinsky L, Kirichok Y, Ramsey IS, Quill TA, Clapham DE. All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc Natl Acad Sci U S A 2007; 104:1219-23. PubMed
  • Xu H, Delling M, Jun JC, Clapham DE. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 2006; 9:628-635. PubMed
  • Ramsey IS, Moran MM, Chong JA, Clapham DE. A voltage-gated proton-selective channel lacking the pore domain. Nature 2006; 440:1213-6. PubMed
  • Kirichok Y, Navarro B, Clapham DE. Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel. Nature 2006; 439:737-40. PubMed
  • Oancea E, Wolfe JT, Clapham DE. Functional TRPM7 channels accumulate at the plasma membrane in response to fluid flow. Circ Res 2005; 98:245-53. PubMed
  • Ramsey IS, Delling M, Clapham DE. An introduction to trp channels. Annu Rev Physiol 2006; 68:619-47. PubMed
  • Clapham DE, Garbers DL. International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels. Pharmacol Rev 2005; 57:451-4. PubMed
  • Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 2005; 57:427-50. PubMed
  • Desai BN, Clapham DE. TRP channels and mice deficient in TRP channels. Pflugers Arch 2005; 451:11-8. PubMed
  • Xu H, Blair NT, Clapham DE. Camphor activates and strongly desensitizes the transient receptor potential vanilloid subtype 1 channel in a vanilloid-independent mechanism. J Neurosci 2005; 25:8924-37. PubMed
  • Chong JA, Moran MM, Teichmann M, Kaczmarek JS, Roeder R, Clapham DE. TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription: reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP. Mol Cell Biol 2005; 25:2632-43. PubMed
  • Zhuang ZY, Xu H, Clapham DE, Ji RR. Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 2004; 24:8300-9. PubMed
  • Krapivinsky G, Medina I, Krapivinsky L, Gapon S, Clapham DE. SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation. Neuron 2004; 43:563-74. PubMed
  • Bezzerides VJ, Ramsey IS, Kotecha S, Greka A, Clapham DE. Rapid vesicular translocation and insertion of TRP channels. Nat Cell Biol 2004; 6:709-20. PubMed
  • Ito M, Xu H, Guffanti AA, Wei Y, Zvi L, Clapham DE, Krulwich TA. The voltage-gated Na+ channel NaVBP has a role in motility, chemotaxis, and pH homeostasis of an alkaliphilic Bacillus. Proc Natl Acad Sci U S A 2004; 101:10566-71. PubMed
  • Moran MM, Xu H, Clapham DE. TRP ion channels in the nervous system. Curr Opin Neurobiol 2004; 14:362-9. PubMed
  • Koishi R, Xu H, Ren D, Navarro B, Spiller BW, Shi Q, Clapham DE. A superfamily of voltage-gated sodium channels in bacteria. J Biol Chem 2003; 279:9532-8. PubMed
  • Xu H, Jin J, DeFelice LJ, Andrews NC, Clapham DE. A Spontaneous, Recurrent Mutation in Divalent Metal Transporter-1 Exposes a Calcium Entry Pathway. PLoS Biol 2004; 2:E50. PubMed
  • Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 2004; 427:360-4. PubMed
  • Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE, Hille B, Garbers DL, Babcock DF. CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proc Natl Acad Sci U S A 2003; 100:14864-8. PubMed
  • Clapham DE. TRP channels as cellular sensors. Nature 2003; 426:517-24. PubMed
  • Krapivinsky G, Krapivinsky L, Manasian Y, Ivanov A, Tyzio R, Pellegrino C, Ben-Ari Y, Clapham DE, Medina I. The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron 2003; 40:775-84. PubMed
  • Str. Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 2003; 278:39014-9. PubMed
  • Greka A, Navarro B, Oancea E, Duggan A, Clapham DE. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nat Neurosci 2003; 6:837-45. PubMed
  • Oancea E, Bezzerides VJ, Greka A, Clapham DE. Mechanism of persistent protein kinase D1 translocation and activation. Dev Cell 2003; 4:561-74. PubMed
  • Wei X, Henke VG, Str. Real-time imaging of nuclear permeation by EGFP in single intact cells. Biophys J 2003; 84:1317-27. PubMed
  • Sandler VM, Wang S, Angelo K, Lo HG, Breakefield XO, Clapham DE. Modified herpes simplex virus delivery of enhanced GFP into the central nervous system. J Neurosci Methods 2002; 121:211-9. PubMed
  • Yue L, Navarro B, Ren D, Ramos A, Clapham DE. The cation selectivity filter of the bacterial sodium channel, NaChBac. J Gen Physiol 2002; 120:845-53. PubMed
  • Clapham DE. Sorting out MIC, TRP, and CRAC ion channels. J Gen Physiol 2002; 120:217-20. PubMed
  • Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, Ge P, Lilly J, Silos-Santiago I, Xie Y, DiStefano PS, Curtis R, Clapham DE. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 2002; 418:181-6. PubMed
  • Runnels LW, Yue L, Clapham DE. The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol 2002; 4:329-36. PubMed
  • Clapham DE. Signal transduction. Hot and cold TRP ion channels. Science 2002; 295:2228-9. PubMed
  • Wickman K, Pu WT, Clapham DE. Structural characterization of the mouse Girk genes. Gene 2002; 284:241-50. PubMed
  • Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX. A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 2002; 9:229-31. PubMed
  • Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE. A prokaryotic voltage-gated sodium channel. Science 2001; 294:2372-5. PubMed
  • Quill TA, Ren D, Clapham DE, Garbers DL. A voltage-gated ion channel expressed specifically in spermatozoa. Proc Natl Acad Sci U S A 2001; 98:12527-31. PubMed
  • Ren D, Navarro B, Perez G, Jackson AC, Hsu S, Shi Q, Tilly JL, Clapham DE. A sperm ion channel required for sperm motility and male fertility. Nature 2001; 413:603-9. PubMed
  • Kovoor P, Wickman K, Maguire CT, Pu W, Gehrmann J, Berul CI, Clapham DE. Evaluation of the role of I(KACh) in atrial fibrillation using a mouse knockout model. J Am Coll Cardiol 2001; 37:2136-43. PubMed
  • Clapham DE, Runnels LW, Str. The TRP ion channel family. Nat Rev Neurosci 2001; 2:387-96. PubMed
  • Hsu Sf , O'Connell PJ, Klyachko VA, Badminton MN, Thomson AW, Jackson MB, Clapham DE, Ahern GP. Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major Ca2+ entry pathway. J Immunol 2001; 166:6126-33. PubMed
  • Corey S, Clapham DE. The Stoichiometry of Gbeta gamma binding to G-protein-regulated inwardly rectifying K+ channels (GIRKs). J Biol Chem 2001; 276:11409-13. PubMed
  • Yue L, Peng JB, Hediger MA, Clapham DE. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature 2001; 410:705-9. PubMed
  • Str. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 2001; 29:645-55. PubMed
  • Runnels LW, Yue L, Clapham DE. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science 2001; 291:1043-7. PubMed
  • Jelacic TM, Kennedy ME, Wickman K, Clapham DE. Functional and biochemical evidence for G-protein-gated inwardly rectifying K+ (GIRK) channels composed of GIRK2 and GIRK3. J Biol Chem 2000; 275:36211-6. PubMed
  • Medina I, Krapivinsky G, Arnold S, Kovoor P, Krapivinsky L, Clapham DE. A switch mechanism for G beta gamma activation of I(KACh). J Biol Chem 2000; 275:29709-16. PubMed
  • Wickman K, Karschin C, Karschin A, Picciotto MR, Clapham DE. Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4. J Neurosci 2000; 20:5608-15. PubMed
  • Franco-Obreg. Distinct ion channel classes are expressed on the outer nuclear envelope of T- and B-lymphocyte cell lines. Biophys J 2000; 79:202-14. PubMed
  • Pu WT, Wickman K, Clapham DE. ICln is essential for cellular and early embryonic viability. J Biol Chem 2000; 275:12363-6. PubMed
  • Wang H, Clapham DE. Conformational changes of the in situ nuclear pore complex. Biophys J 1999; 77:241-7. PubMed
  • Pu WT, Krapivinsky GB, Krapivinsky L, Clapham DE. pICln inhibits snRNP biogenesis by binding core spliceosomal proteins. Mol Cell Biol 1999; 19:4113-20. PubMed
  • Clapham DE. Unlocking family secrets: K+ channel transmembrane domains. Cell 1999; 97:547-50. PubMed
  • Jelacic TM, Sims SM, Clapham DE. Functional expression and characterization of G-protein-gated inwardly rectifying K+ channels containing GIRK3. J Membr Biol 1999; 169:123-9. PubMed
  • Arnold DB, Clapham DE. Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel. Neuron 1999; 23:149-57. PubMed
  • Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE. Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh. Ann N Y Acad Sci 1999; 868:386-98. PubMed
  • Kennedy ME, Nemec J, Corey S, Wickman K, Clapham DE. GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels. J Biol Chem 1999; 274:2571-82. PubMed
  • Nemec J, Wickman K, Clapham DE. Gbetagamma binding increases the open time of IKACh: kinetic evidence for multiple Gbetagamma binding sites. Biophys J 1999; 76:246-52. PubMed
  • Corey S, Clapham DE. Identification of native atrial G-protein-regulated inwardly rectifying K+ (GIRK4) channel homomultimers. J Biol Chem 1998; 273:27499-504. PubMed
  • Krapivinsky G, Kennedy ME, Nemec J, Medina I, Krapivinsky L, Clapham DE. Gbeta binding to GIRK4 subunit is critical for G protein-gated K+ channel activation. J Biol Chem 1998; 273:16946-52. PubMed
  • Krapivinsky G, Medina I, Eng L, Krapivinsky L, Yang Y, Clapham DE. A novel inward rectifier K+ channel with unique pore properties. Neuron 1998; 20:995-1005. PubMed
  • Krapivinsky G, Pu W, Wickman K, Krapivinsky L, Clapham DE. pICln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology. J Biol Chem 1998; 273:10811-4. PubMed
  • Lorenz E, Alekseev AE, Krapivinsky GB, Carrasco AJ, Clapham DE, Terzic A. Evidence for direct physical association between a K+ channel (Kir6.2) and an ATP-binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K+ channel. Mol Cell Biol 1998; 18:1652-9. PubMed
  • Corey S, Krapivinsky G, Krapivinsky L, Clapham DE. Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh. J Biol Chem 1998; 273:5271-8. PubMed
  • Lee MA, Dunn RC, Clapham DE, Stehno-Bittel L. Calcium regulation of nuclear pore permeability. Cell Calcium 1998; 23:91-101. PubMed
  • Wickman K, Nemec J, Gendler SJ, Clapham DE. Abnormal heart rate regulation in GIRK4 knockout mice. Neuron 1998; 20:103-14. PubMed
  • Perez-Terzic C, Jaconi M, Clapham DE. Nuclear calcium and the regulation of the nuclear pore complex. Bioessays 1997; 19:787-92. PubMed
  • Wickman K, Seldin MF, Gendler SJ, Clapham DE. Partial structure, chromosome localization, and expression of the mouse Girk4 gene. Genomics 1997; 40:395-401. PubMed
  • Wickman K, Seldin MF, James MR, Gendler SJ, Clapham DE. Partial structure, chromosome localization, and expression of the mouse Icln gene. Genomics 1997; 40:402-8. PubMed
  • Perez-Terzic C, Pyle J, Jaconi M, Stehno-Bittel L, Clapham DE. Conformational states of the nuclear pore complex induced by depletion of nuclear Ca2+ stores. Science 1996; 273:1875-7. PubMed
  • Navarro B, Kennedy ME, Velimirov. Nonselective and G betagamma-insensitive weaver K+ channels. Science 1996; 272:1950-3. PubMed
  • Velimirovic BM, Gordon EA, Lim NF, Navarro B, Clapham DE. The K+ channel inward rectifier subunits form a channel similar to neuronal G protein-gated K+ channel. FEBS Lett 1996; 379:31-7. PubMed
  • Kennedy ME, Nemec J, Clapham DE. Localization and interaction of epitope-tagged GIRK1 and CIR inward rectifier K+ channel subunits. Neuropharmacology 1996; 35:831-9. PubMed
  • Stehno-Bittel L, Krapivinsky G, Krapivinsky L, Perez-Terzic C, Clapham DE. The G protein beta gamma subunit transduces the muscarinic receptor signal for Ca2+ release in Xenopus oocytes. J Biol Chem 1995; 270:30068-74. PubMed
  • Krapivinsky G, Krapivinsky L, Wickman K, Clapham DE. G beta gamma binds directly to the G protein-gated K+ channel, IKACh. J Biol Chem 1995; 270:29059-62. PubMed
  • Krapivinsky G, Krapivinsky L, Velimirovic B, Wickman K, Navarro B, Clapham DE. The cardiac inward rectifier K+ channel subunit, CIR, does not comprise the ATP-sensitive K+ channel, IKATP. J Biol Chem 1995; 270:28777-9. PubMed
  • Krapivinsky G, Gordon EA, Wickman K, Velimirovic B, Krapivinsky L, Clapham DE. The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins. Nature 1995; 374:135-41. PubMed
  • Stehno-Bittel L, L. Calcium release from the nucleus by InsP3 receptor channels. Neuron 1995; 14:163-7. PubMed
  • L. Calcium channels activated by depletion of internal calcium stores in A431 cells. Biophys J 1994; 67:177-82. PubMed
  • Wickman KD, I. Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel. Nature 1994; 368:255-7. PubMed
  • Krapivinsky GB, Ackerman MJ, Gordon EA, Krapivinsky LD, Clapham DE. Molecular characterization of a swelling-induced chloride conductance regulatory protein, pICln. Cell 1994; 76:439-48. PubMed
  • Ackerman MJ, Wickman KD, Clapham DE. Hypotonicity activates a native chloride current in Xenopus oocytes. J Gen Physiol 1994; 103:153-79. PubMed
  • Clapham DE, Lechleiter JD, Girard S. Intracellular waves observed by confocal microscopy from Xenopus oocytes. Adv Second Messenger Phosphoprotein Res 1993; 28:161-5. PubMed
  • Lechleiter JD, Clapham DE. Molecular mechanisms of intracellular calcium excitability in X. laevis oocytes. Cell 1992; 69:283-94. PubMed
  • L. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. Nature 1992; 355:356-8. PubMed
  • Lechleiter JD, Clapham DE. Spiral waves and intracellular calcium signalling. J Physiol Paris 1992; 86:123-8. PubMed
  • Wallert MA, Ackerman MJ, Kim D, Clapham DE. Two novel cardiac atrial K+ channels, IK.AA and IK.PC. J Gen Physiol 1991; 98:921-39. PubMed
  • Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle WA, Nerbonne JM, Peralta EG, Clapham DE. Cloning and expression of a rat cardiac delayed rectifier potassium channel. Proc Natl Acad Sci U S A 1991; 88:7892-5. PubMed
  • Tabares L, Mazzanti M, Clapham DE. Chloride channels in the nuclear membrane. J Membr Biol 1991; 123:49-54. PubMed
  • Clapham DE. Arachidonic acid and its metabolites in the regulation of G-protein gated K+ channels in atrial myocytes. Biochem Pharmacol 1990; 39:813-5. PubMed
  • Nanavati C, Clapham DE, Ito H, Kurachi Y. A comparison of the roles of purified G protein subunits in the activation of the cardiac muscarinic K+ channel. Soc Gen Physiol Ser 1990; 45:29-41. PubMed
  • Lewis DL, Clapham DE. Somatostatin activates an inwardly rectifying K+ channel in neonatal rat atrial cells. Pflugers Arch 1989; 414:492-4. PubMed
  • Kim D, Clapham DE. Potassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 1989; 244:1174-6. PubMed
  • Kim D, Lewis DL, Graziadei L, Neer EJ, Bar-Sagi D, Clapham DE. G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature 1989; 337:557-60. PubMed
  • Clapham DE, Kim D. G protein activation mechanisms of the cardiac K+ channel, iK.ACh. Soc Gen Physiol Ser 1988; 44:55-68. PubMed
  • Logothetis DE, Kim DH, Northup JK, Neer EJ, Clapham DE. Specificity of action of guanine nucleotide-binding regulatory protein subunits on the cardiac muscarinic K+ channel. Proc Natl Acad Sci U S A 1988; 85:5814-8. PubMed
  • Neer EJ, Clapham DE. Roles of G protein subunits in transmembrane signalling. Nature 1988; 333:129-34. PubMed
  • Fish RD, Sperti G, Colucci WS, Clapham DE. Phorbol ester increases the dihydropyridine-sensitive calcium conductance in a vascular smooth muscle cell line. Circ Res 1988; 62:1049-54. PubMed
  • Olesen SP, Clapham DE, Davies PF. Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 1988; 331:168-70. PubMed
  • Clapham DE, Logothetis DE. Delayed rectifier K+ current in embryonic chick heart ventricle. Am J Physiol 1987; 254:H192-7. PubMed
  • Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE. The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 1987; 325:321-6. PubMed
  • Bormann J, Clapham DE. gamma-Aminobutyric acid receptor channels in adrenal chromaffin cells: a patch-clamp study. Proc Natl Acad Sci U S A 1985; 82:2168-72. PubMed
  • Ypey DL, Clapham DE. Development of a delayed outward-rectifying K+ conductance in cultured mouse peritoneal macrophages. Proc Natl Acad Sci U S A 1984; 81:3083-7. PubMed
  • Clapham DE, Neher E. Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells. J Physiol 1984; 347:255-77. PubMed
  • Clapham DE, DeFelice LJ. Small signal impedance of heart cell membranes. J Membr Biol 1981; 67:63-71. PubMed
  • Clapham DE, Shrier A, DeHaan RL. Junctional resistance and action potential delay between embryonic heart cell aggregates. J Gen Physiol 1980; 75:633-54. PubMed
  • Ypey DL, Clapham DE, DeHaan RL. Development of electrical coupling and action potential synchrony between paired aggregates of embryonic heart cells. J Membr Biol 1979; 51:75-96. PubMed
  • Clapham DE, De Felice LJ. The theoretical small signal impedance of the frog node, Rana pipiens. Pflugers Arch 1976; 366:273-6. PubMed
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