Fields of Research
- Electrical Signaling Mechanisms in Nerve and Muscle
- Structure of Voltage Gated Sodium and Calcium Channels
- Ion Channel Regulation and Ion Channelopathies
- Molecular Pharmacology of Ion Channels
- Molecular Mechanisms in Epilepsy, Autism,
and Heart Failure
Electrical signaling initiates all fast events in biology from bacteria to man. We study the structural basis for electrical signaling at the atomic level, and we investigate diseases caused by failure of electrical signaling.
Electrical signaling is crucial for sensation, learning, memory, hormonal regulation, movement, and many other processes from single-celled organisms to man. We study the voltage-gated sodium and calcium channels that initiate action potential generation and synaptic transmission in nerve and muscle cells. We discovered these channel proteins in the 1980’s, analyzed their structure and function in the 1990’s and 2000’s, and determined their structures at atomic resolution using X-ray crystallography and cryo-electron microscopy in the past decade. We now probe their mechanisms of voltage-dependent gating, ion conductance and selectivity, pharmacological modulation, and second-messenger regulation in atomic detail. Recent studies have revealed the complete conformational cycle for sodium channel gating, the mechanism of action of mutations that cause periodic paralysis, and the sites and mechanisms of action of the local anesthetic and antiarrhythmic drugs that block sodium channels and the calcium antagonist drugs that block calcium channels. We also study ion channelopathies that are caused by mutations and dysregulation of voltage-gated sodium and calcium channels in the context of periodic paralysis, cardiac arrhythmia, epilepsy, and autism, using a combination of electrophysiology, molecular and structural biology, mouse genetics, and behavior.
Awards and Honors
NINDS, NIH (PI)
NHLBI, NIH (Sole PI)
Simons Foundation (Co-PI)
Air Force Office of Scientific Research (Co-PI)
Fellow of the American Society for Pharmacology & Experimental Therapeutics
Awards and Academies (Selected)
Member, National Academy of Science
Member, National Academy of Medicine
Fellow, American Academy of Arts & Sciences
Fellow, American Association for the Advancement of Science
Foreign Member, Royal Society of London
Foreign Member, Academia Europaea
American Heart Association Basic Research Award
Bristol Myers Squibb Award for Distinguished Research in Neuroscience
K. S. Cole Award, Biophysical Society
Gairdner International Award of Canada
Robert Ruffolo Career Achievement Award, American Society for Pharmacology & Experimental Therapeutics
Pioneer Award, Winter Conference on Brain Research
- Health Sciences Building
- Health Sciences Building
Pharmacy: Phcol 402
Graduate: Phcol 511, Phcol 512
Graduate Research Seminar: Phcol 529
Natasha Powell (Neuro grad student)
Liam Hovey (MD/PhD grad student)
Shu-Hui Chuang (Postdoctoral fellow)
Lige Tonggu (Postdoctoral fellow)
Alaeddine Djillani (Postdoctoral fellow)
Daohua Jiang (Postdoctoral fellow)
George Wisedchaisri (Acting Assistant Professor)
Tamer Gamal El-Din (Research Assistant Professor)
Michael Lenaeus (Assistant Professor of Medicine)
Ruth Westenbroek (Research Associate Professor)
Jin Li (Research Scientist 3, Lab Manager)
Tim Lantin (Research Scientist 1)
Wisedchaisri G, Tonggu L, McCord E, Gamal El-Din TM, Wang L, Zheng N, Catterall WA. (2019) Resting state structure and gating mechanism of a voltage-gated sodium channel. Cell Jul 17. ePub ahead of print. PMID: 31353218.
Nanou E, Lee A, Catterall WA. (2018) Control of excitation/inhibition balance in a hippocampal circuit by calcium sensor protein regulation of presynaptic calcium channels. J Neurosci. 38:4430-4440. PMID: 29654190; PMCID: PMC5932646.
Jiang D, Gamal El-Din TM, Ing C, Lu P, Pomès R, Zheng N, Catterall WA. (2018) Structural basis for gating pore current in periodic paralysis. Nature 557:590-594. PMID: 29769724.
Lenaeus MJ, Gamal El-Din TM, Ing C, Ramanadane K, Pomès R, Zheng N, Catterall WA. (2017) Structures of closed and open states of a voltage-gated sodium channel. Proc Natl Acad Sci USA. 114:E3051-E3060. PubMed PMID: 28348242; PMCID: PMC5393245.
Tang L, El-Din TM, Swanson TM, Pryde DC, Scheuer T, Zheng N, Catterall WA. (2016) Structural basis for inhibition of a voltage-gated Ca2+ channel by Ca2+ antagonist drugs. Nature 537:117-121 PMID: 27556947; PMCID: PMC5161592.
Yang L, Dai DF, Yuan C, Westenbroek RE, Yu H, West N, de la Iglesia HO, Catterall WA. (2016) Loss of .-adrenergic-stimulated phosphorylation of Cav1.2 channels on Ser1700 leads to heart failure. Proc Natl Acad Sci USA. 113:E7976-E7985. PMID: 27864509; PMCID: PMC5150375.
Rubinstein M, Han S, Tai C, Westenbroek RE, Hunker A, Scheuer T, Catterall WA. (2015) Dissecting the phenotypes of Dravet syndrome by gene deletion. Brain 138:2219-2233. PMID: 26017580; PMCID: PMC5022661.
Tang L, Gamal El-Din TM, Payandeh J, Martinez GQ, Heard TM, Scheuer T, Zheng N, Catterall WA. (2014) Structural basis for Ca2+ selectivity of a voltage-gated calcium channel. Nature 505:56-61. PMID: 24270805; PMCID: PMC3877713. Research Article.
Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. (2014) Enhancement of inhibitory neurotransmission by GABAA receptors having .2,3-subunits ameliorates behavioral deficits in a mouse model of autism. Neuron 81:1282-1289. PMID: 24656250; PMCID:PMC4079471.
Payandeh J, Gamal El-Din TM, Scheuer T, Zheng N, and Catterall WA (2012) Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. Nature 486:135-139. PMID: 22678296.
Han S, Tai C, Westenbroek RE, Yu FH, Cheah CS, Potter GB, Rubenstein JL, Scheuer T, de la Iglesia HO, Catterall WA. 2012Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489:385-390. PMID:22914087; PMCID: PMC3448848. Research Article.
Cheah CS, Yu FH, Westenbroek RE, Kalume FK, Oakley JC, Potter GB, Rubenstein JL, Catterall WA. (2012) Specific deletion of NaV1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome. Proc Natl Acad Sci USA. 109:14646-14651. PMID: 22908258; PMCID: PMC3437823.
Payandeh J, Scheuer T, Zheng N, and Catterall WA. (2011) Crystal structure of a voltage-gated sodium channel. Nature 475:353-358. PMID: 21743477. Research Article.