 |
||||
|
||||
|
||||
|
||||
.gif?ad=17923&adview=true)
The Journal of Neuroscience, December 10, 2003, 23(36):11289-11295
Previous Article | Next Article
Cellular/Molecular
Epilepsy-Associated Dysfunction in the Voltage-Gated Neuronal Sodium Channel SCN1A
Christoph Lossin,1 Thomas H. Rhodes,2 Reshma R. Desai,2 Carlos G. Vanoye,2 Dao Wang,3 Sanda Carniciu,4 Orrin Devinsky,4 andAlfred L. George, Jr2,3 1Neuroscience Graduate Program, 2Division of Genetic Medicine, Department of Medicine, and 3Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-0275, and 4Department of Neurology, New York University, New York, New York 10016
Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel
1 subunit (NaV1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density and accelerated recovery from slow inactivation. Unlike three other GEFS+ alleles that we recently characterized, neither R1657C nor I1656M gave rise to a persistent, noninactivating current. In contrast, two other GEFS+ mutations (A1685V and V1353L) and L986F, an SMEI-associated allele, exhibited complete loss of function. In conclusion, our data provide evidence for a wide spectrum of sodium channel dysfunction in familial epilepsy and demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1A alleles.
Key words: epilepsy; sodium channel; GEFS+; SMEI; SCN1A; electrophysiology
Received Sep 2, 2003; revised October 9, 2003; accepted October 9, 2003.
This article has been cited by other articles:
K. M. Kahlig, T. H. Rhodes, M. Pusch, T. Freilinger, J. M. Pereira-Monteiro, M. D. Ferrari, A. M. J. M. van den Maagdenberg, M. Dichgans, and A. L. George Jr.
Divergent sodium channel defects in familial hemiplegic migraine
PNAS, July 15, 2008; 105(28): 9799 - 9804.
[Abstract] [Full Text] [PDF]
J. Szendroedi, W. Sandtner, T. Zarrabi, E. Zebedin, K. Hilber, S. C. Dudley Jr., H. A. Fozzard, and H. Todt
Speeding the Recovery from Ultraslow Inactivation of Voltage-Gated Na+ Channels by Metal Ion Binding to the Selectivity Filter: A Foot-on-the-Door?
Biophys. J., December 15, 2007; 93(12): 4209 - 4224.
[Abstract] [Full Text] [PDF]
R. Rusconi, P. Scalmani, R. R. Cassulini, G. Giunti, A. Gambardella, S. Franceschetti, G. Annesi, E. Wanke, and M. Mantegazza
Modulatory Proteins Can Rescue a Trafficking Defective Epileptogenic Nav1.1 Na+ Channel Mutant
J. Neurosci., October 10, 2007; 27(41): 11037 - 11046.
[Abstract] [Full Text] [PDF]
I. Ogiwara, H. Miyamoto, N. Morita, N. Atapour, E. Mazaki, I. Inoue, T. Takeuchi, S. Itohara, Y. Yanagawa, K. Obata, et al.
Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: A Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation
J. Neurosci., May 30, 2007; 27(22): 5903 - 5914.
[Abstract] [Full Text] [PDF]
T. P. Harty, S. D. Dib-Hajj, L. Tyrrell, R. Blackman, F. M. Hisama, J. B. Rose, and S. G. Waxman
Nav1.7 Mutant A863P in Erythromelalgia: Effects of Altered Activation and Steady-State Inactivation on Excitability of Nociceptive Dorsal Root Ganglion Neurons
J. Neurosci., November 29, 2006; 26(48): 12566 - 12575.
[Abstract] [Full Text] [PDF]
K. M. Kahlig, S. N. Misra, and A. L. George Jr
Impaired Inactivation Gate Stabilization Predicts Increased Persistent Current for an Epilepsy-Associated SCN1A Mutation
J. Neurosci., October 25, 2006; 26(43): 10958 - 10966.
[Abstract] [Full Text] [PDF]
F. Madia, P. Striano, E. Gennaro, M. Malacarne, R. Paravidino, R. Biancheri, M. Budetta, M. R. Cilio, R. Gaggero, M. Pierluigi, et al.
Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy.
Neurology, October 10, 2006; 67(7): 1230 - 1235.
[Abstract] [Full Text] [PDF]
J. A. Kearney, Y. Yang, B. Beyer, S. K. Bergren, L. Claes, P. DeJonghe, and W. N. Frankel
Severe epilepsy resulting from genetic interaction between Scn2a and Kcnq2
Hum. Mol. Genet., March 15, 2006; 15(6): 1043 - 1048.
[Abstract] [Full Text] [PDF]
A. J. Barela, S. P. Waddy, J. G. Lickfett, J. Hunter, A. Anido, S. L. Helmers, A. L. Goldin, and A. Escayg
An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability.
J. Neurosci., March 8, 2006; 26(10): 2714 - 2723.
[Abstract] [Full Text] [PDF]
C. G. Vanoye, C. Lossin, T. H. Rhodes, and A. L. George Jr.
Single-channel Properties of Human NaV1.1 and Mechanism of Channel Dysfunction in SCN1A-associated Epilepsy
J. Gen. Physiol., December 27, 2005; 127(1): 1 - 14.
[Abstract] [Full Text] [PDF]
T. H. Rhodes, C. G. Vanoye, I. Ohmori, I. Ogiwara, K. Yamakawa, and A. L. George Jr
Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures
J. Physiol., December 1, 2005; 569(2): 433 - 445.
[Abstract] [Full Text] [PDF]
J. M. Nerbonne and R. S. Kass
Molecular Physiology of Cardiac Repolarization
Physiol Rev, October 1, 2005; 85(4): 1205 - 1253.
[Abstract] [Full Text] [PDF]
W. Ulbricht
Sodium Channel Inactivation: Molecular Determinants and Modulation
Physiol Rev, October 1, 2005; 85(4): 1271 - 1301.
[Abstract] [Full Text] [PDF]
J. Turnbull, H. Lohi, J. A. Kearney, G. A. Rouleau, A. V. Delgado-Escueta, M. H. Meisler, P. Cossette, and B. A. Minassian
Sacred disease secrets revealed: the genetics of human epilepsy
Hum. Mol. Genet., September 1, 2005; 14(17): 2491 - 2500.
[Abstract] [Full Text] [PDF]
I. Vitko, Y. Chen, J. M. Arias, Y. Shen, X.-R. Wu, and E. Perez-Reyes
Functional Characterization and Neuronal Modeling of the Effects of Childhood Absence Epilepsy Variants of CACNA1H, a T-Type Calcium Channel
J. Neurosci., May 11, 2005; 25(19): 4844 - 4855.
[Abstract] [Full Text] [PDF]
J. Spampanato, J. A. Kearney, G. de Haan, D. P. McEwen, A. Escayg, I. Aradi, B. T. MacDonald, S. I. Levin, I. Soltesz, P. Benna, et al.
A Novel Epilepsy Mutation in the Sodium Channel SCN1A Identifies a Cytoplasmic Domain for {beta} Subunit Interaction
J. Neurosci., November 3, 2004; 24(44): 10022 - 10034.
[Abstract] [Full Text] [PDF]
T. H. Rhodes, C. Lossin, C. G. Vanoye, D. W. Wang, and A. L. George Jr.
Noninactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy
PNAS, July 27, 2004; 101(30): 11147 - 11152.
[Abstract] [Full Text] [PDF]
A. L. George Jr
Molecular Basis of Inherited Epilepsy
Arch Neurol, April 1, 2004; 61(4): 473 - 478.
[Full Text] [PDF]
C. E. Clancy and R. S. Kass
Theoretical Investigation of the Neuronal Na+ Channel SCN1A: Abnormal Gating and Epilepsy
Biophys. J., April 1, 2004; 86(4): 2606 - 2614.
[Abstract] [Full Text] [PDF]
K. Kamiya, M. Kaneda, T. Sugawara, E. Mazaki, N. Okamura, M. Montal, N. Makita, M. Tanaka, K. Fukushima, T. Fujiwara, et al.
A Nonsense Mutation of the Sodium Channel Gene SCN2A in a Patient with Intractable Epilepsy and Mental Decline
J. Neurosci., March 17, 2004; 24(11): 2690 - 2698.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|