Steve Cannon, M.D., Ph.D.

Chair, Physiology Member, CTSI Molecular, Cellular & Integrative Physiology GPB Home Area

sccannon@mednet.ucla.edu

310-825-4463

543-263B CHS
CA
UNITED STATES

Biography

The primary research interests of our laboratory are how ion channels regulate the electrical excitability of cells and how defects in these channels lead to human disease. In the past two decades, mutations of ion channel genes have been found to be the primary cause for over 100 human diseases. Our research program is focused on the mechanistic basis for a group of inherited conditions that alter the electrical excitability of skeletal muscle, including periodic paralysis and myotonia. We have characterized the gating defects of mutant channels, generated computational models of muscle excitability, and produced genetically-engineered mice to gain insights on the pathomechanisms of these disorders and to explore therapeutic interventions.

Awards and Honors

Derek Denny-Brown Neurological Scholar, Massachusetts General Hospital, 2000.
Paul Horowicz Endowed Lecture, Univresity of Rochester, 2019.
MERIT Award, NIH, UT Southwestern Medical Center, 2008-2018.
Regents Outstanding Teaching Award, UT Southwestern Medical Center, 2014.
Biophysical Society Award in the Biophysics of Health and Disease, UCLA, 2022.
Linda and Mitch Hart Distinguished Chair in Neurology, UT Southwestern Medical Center, 2002.

Publications

Quiñonez M, DiFranco M, Wu F, Cannon SC. Retigabine suppresses loss of force in mouse models of hypokalaemic periodic paralysis.. Brain : a journal of neurology, 2023.
DiFranco M, Cannon SC. Voltage-dependent Ca2+ release is impaired in hypokalemic periodic paralysis caused by CaV1.1-R528H but not by NaV1.4-R669H.. American journal of physiology. Cell physiology, 2022.
Savalli N, Angelini M, Steccanella F, Wier J, Wu F, Quinonez M, DiFranco M, Neely A, Cannon SC, Olcese R. The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation.. The Journal of general physiology, 2021.
Wu F, Quinonez M, Cannon SC. Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP.. The Journal of general physiology, 2021.
Cannon SC. Epilepsy channelopathies go neddy: stabilizing NaV1.1 channels by neddylation.. The Journal of clinical investigation, 2021.
Kubota T, Wu F, Vicart S, Nakaza M, Sternberg D, Watanabe D, Furuta M, Kokunai Y, Abe T, Kokubun N, Fontaine B, Cannon SC, Takahashi MP. Hypokalaemic periodic paralysis with a charge-retaining substitution in the voltage sensor.. Brain communications, 2020.
Cannon SC. A role for external Ca2+ in maintaining muscle contractility in periodic paralysis.. The Journal of general physiology, 2020.
Stunnenberg BC, LoRusso S, Arnold WD, Barohn RJ, Cannon SC, Fontaine B, Griggs RC, Hanna MG, Matthews E, Meola G, Sansone VA, Trivedi JR, van Engelen BGM, Vicart S, Statland JM. Guidelines on clinical presentation and management of nondystrophic myotonias.. Muscle & nerve, 2020.
Elia N, Nault T, McMillan HJ, Graham GE, Huang L, Cannon SC. Corrigendum: Myotonic Myopathy With Secondary Joint and Skeletal Anomalies From the c.2386C>G, p.L796V Mutation in SCN4A.. Frontiers in neurology, 2020.
Cannon SC. Further evidence for shared genetic susceptibility in both sporadic and Thyrotoxic periodic paralysis.. Journal of the neurological sciences, 2020.
Elia N, Nault T, McMillan HJ, Graham GE, Huang L, Cannon SC. Myotonic Myopathy With Secondary Joint and Skeletal Anomalies From the c.2386C>G, p.L769V Mutation in SCN4A.. Frontiers in neurology, 2020.
DiFranco M, Quinonez M, Dziedzic RM, Spokoyny AM, Cannon SC. A highly-selective chloride microelectrode based on a mercuracarborand anion carrier.. Scientific reports, 2019.
Mason ER, Wu F, Patel RR, Xiao Y, Cannon SC, Cummins TR. Resurgent and Gating Pore Currents Induced by De Novo SCN2A Epilepsy Mutations.. eNeuro, 2019.
Heiny JA, Cannon SC, DiFranco M. A four-electrode method to study dynamics of ion activity and transport in skeletal muscle fibers.. The Journal of general physiology, 2019.
Elia N, Palmio J, Castañeda MS, Shieh PB, Quinonez M, Suominen T, Hanna MG, Männikkö R, Udd B, Cannon SC. Myasthenic congenital myopathy from recessive mutations at a single residue in NaV1.4.. Neurology, 2019.
Mi W, Wu F, Quinonez M, DiFranco M, Cannon SC. Recovery from acidosis is a robust trigger for loss of force in murine hypokalemic periodic paralysis.. The Journal of general physiology, 2019.
Cannon SC. Skeletal muscle channelopathy: a new risk for sudden infant death syndrome.. Lancet (London, England), 2018.
Lin MA, Cannon SC, Papazian DM. Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.. Proceedings of the National Academy of Sciences of the United States of America, 2018.
Wu F, Quinonez M, DiFranco M, Cannon SC. Stac3 enhances expression of human CaV1.1 in Xenopus oocytes and reveals gating pore currents in HypoPP mutant channels.. The Journal of general physiology, 2018.
Cannon SC. Sodium Channelopathies of Skeletal Muscle.. Handbook of experimental pharmacology, 2018.
Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, Shieh PB, Tawil RN, Trivedi J, Cannon SC, Griggs RC. Review of the Diagnosis and Treatment of Periodic Paralysis.. Muscle & nerve, 2017.
Cannon SC. An atypical CaV1.1 mutation reveals a common mechanism for hypokalemic periodic paralysis.. The Journal of general physiology, 2017.
Cannon SC. Mind the magnesium, in dantrolene suppression of malignant hyperthermia.. Proceedings of the National Academy of Sciences of the United States of America, 2017.
Wu F, Mi W, Fu Y, Struyk A, Cannon SC. Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.. Brain : a journal of neurology, 2016.
Cannon SC. When all is lost…a severe myopathy with hypotonia from sodium channel mutations.. Brain : a journal of neurology, 2016.
Nelson BR, Makarewich CA, Anderson DM, Winders BR, Troupes CD, Wu F, Reese AL, McAnally JR, Chen X, Kavalali ET, Cannon SC, Houser SR, Bassel-Duby R, Olson EN. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle.. Science (New York, N.Y.), 2016.
Cannon SC. Channelopathies of skeletal muscle excitability.. Comprehensive Physiology, 2015.
Mi W, Rybalchenko V, Cannon SC. Disrupted coupling of gating charge displacement to Na+ current activation for DIIS4 mutations in hypokalemic periodic paralysis.. The Journal of general physiology, 2014.
Trivedi JR, Cannon SC, Griggs RC. Nondystrophic myotonia: challenges and future directions.. Experimental neurology, 2013.
Wu F, Mi W, Cannon SC. Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis.. Brain : a journal of neurology, 2013.
Nelson BR, Wu F, Liu Y, Anderson DM, McAnally J, Lin W, Cannon SC, Bassel-Duby R, Olson EN. Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
Wu F, Mi W, Cannon SC. Bumetanide prevents transient decreases in muscle force in murine hypokalemic periodic paralysis.. Neurology, 2013.
Wu F, Mi W, Hernández-Ochoa EO, Burns DK, Fu Y, Gray HF, Struyk AF, Schneider MF, Cannon SC. A calcium channel mutant mouse model of hypokalemic periodic paralysis.. The Journal of clinical investigation, 2012.
Cannon SC. Small fiber neuropathy: a bit less idiopathic?. Neurology, 2012.
Wu F, Mi W, Burns DK, Fu Y, Gray HF, Struyk AF, Cannon SC. A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis.. The Journal of clinical investigation, 2011.
Kudryashova E, Struyk A, Mokhonova E, Cannon SC, Spencer MJ. The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype.. Human molecular genetics, 2011.
Cheng CJ, Lin SH, Lo YF, Yang SS, Hsu YJ, Cannon SC, Huang CL. Identification and functional characterization of Kir2.6 mutations associated with non-familial hypokalemic periodic paralysis.. The Journal of biological chemistry, 2011.
Francis DG, Rybalchenko V, Struyk A, Cannon SC. Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.. Neurology, 2011.
Cannon SC. Voltage-sensor mutations in channelopathies of skeletal muscle.. The Journal of physiology, 2010.
Cannon SC, Bean BP. Sodium channels gone wild: resurgent current from neuronal and muscle channelopathies.. The Journal of clinical investigation, 2009.
Cannon SC. Getting a charge out of periodic paralysis?. Neurology, 2009.
Webb J, Wu FF, Cannon SC. Slow inactivation of the NaV1.4 sodium channel in mammalian cells is impeded by co-expression of the beta1 subunit.. Pflugers Archiv : European journal of physiology, 2008.
Struyk AF, Markin VS, Francis D, Cannon SC. Gating pore currents in DIIS4 mutations of NaV1.4 associated with periodic paralysis: saturation of ion flux and implications for disease pathogenesis.. The Journal of general physiology, 2008.
Hayward LJ, Kim JS, Lee MY, Zhou H, Kim JW, Misra K, Salajegheh M, Wu FF, Matsuda C, Reid V, Cros D, Hoffman EP, Renaud JM, Cannon SC, Brown RH. Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness.. The Journal of clinical investigation, 2008.
Struyk AF, Cannon SC. Paradoxical depolarization of BA2+- treated muscle exposed to low extracellular K+: insights into resting potential abnormalities in hypokalemic paralysis.. Muscle & nerve, 2008.
Webb J, Cannon SC. Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia.. Neurology, 2007.
Struyk AF, Cannon SC. A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore.. The Journal of general physiology, 2007.
Cannon SC. Physiologic principles underlying ion channelopathies.. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2007.
Cannon SC. Pathomechanisms in channelopathies of skeletal muscle and brain.. Annual review of neuroscience, 2006.
Wu FF, Gordon E, Hoffman EP, Cannon SC. A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation.. The Journal of physiology, 2005.
Berg J, Jiang H, Thornton CA, Cannon SC. Truncated ClC-1 mRNA in myotonic dystrophy exerts a dominant-negative effect on the Cl current.. Neurology, 2004.
Cannon SC. Paying the price at the pump: dystonia from mutations in a Na+/K+ -ATPase.. Neuron, 2004.
Tsujino A, Maertens C, Ohno K, Shen XM, Fukuda T, Harper CM, Cannon SC, Engel AG. Myasthenic syndrome caused by mutation of the SCN4A sodium channel.. Proceedings of the National Academy of Sciences of the United States of America, 2003.
Struyk AF, Cannon SC. Slow inactivation does not block the aqueous accessibility to the outer pore of voltage-gated Na channels.. The Journal of general physiology, 2002.
Cannon SC. An expanding view for the molecular basis of familial periodic paralysis.. Neuromuscular disorders : NMD, 2002.
Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy.. Molecular cell, 2002.
Cannon SC. Sodium channel gating: no margin for error.. Neuron, 2002.