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Abstract:

Studies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. In this review we focus on the role of mutated Ca V2.1 (i.e., P/Q-type) voltage-activated Ca 2+ channels, and on the ultimate consequences that mutations causing familial hemiplegic migraine type-1 (FHM1) have in neurotransmitter release. Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of Ca V2.1 channels. Mutated Ca V2.1 channels activate at more hyperpolarizing potentials and lead to a gain-of-function in synaptic transmission. This gain-of-function might underlie alterations in the excitatory/ inhibitory balance of synaptic transmission, favoring a persistent state of hyperexcitability in cortical neurons that would increase the susceptibility for cortical spreading depression (CSD), a mechanism believed to initiate the attacks of migraine with aura. © 2011 Elsevier Ltd.

Registro:

Documento: Artículo
Título:Ca V2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis
Autor:Uchitel, O.D.; Inchauspe, C.G.; Urbano, F.J.; Di Guilmi, M.N.
Filiación:Instituto de Fisiología, Biología Molecular y Neurociencias (CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
Palabras clave:Ca V2.1 (P/Q-type) Ca 2+ channels; Cortical spreading depression; Familial hemiplegic migraine; R192Q and S218L knock in mice; Synaptic transmission; calcium channel; calcium channel P type; calcium channel Q type; sodium channel Nav1.1; unclassified drug; voltage activated calcium channel Cav2.1; voltage gated calcium channel; calcium channel N type; voltage dependent calcium channel (P Q type); voltage-dependent calcium channel (P-Q type); article; brain cell; cell function; disease activity; enzyme activation; experimental model; familial hemiplegic migraine; gain of function mutation; gene mutation; human; hyperpolarization; migraine with aura; nerve cell excitability; nerve cell plasticity; neurotransmission; neurotransmitter release; nonhuman; pathogenesis; protein expression; protein function; regulatory mechanism; spreading cortical depression; synapse; synaptic transmission; transgenic mouse; animal; brain cortex; genetics; migraine with aura; mouse; mutation; pathology; pathophysiology; review; Animals; Calcium Channels, N-Type; Cerebral Cortex; Cortical Spreading Depression; Humans; Mice; Mice, Transgenic; Migraine with Aura; Mutation; Synaptic Transmission
Año:2012
Volumen:106
Número:1-2
Página de inicio:12
Página de fin:22
DOI: http://dx.doi.org/10.1016/j.jphysparis.2011.10.004
Título revista:Journal of Physiology Paris
Título revista abreviado:J. Physiol. Paris
ISSN:09284257
CODEN:JHYSE
CAS:Calcium Channels, N-Type; voltage-dependent calcium channel (P-Q type)
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09284257_v106_n1-2_p12_Uchitel

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Citas:

---------- APA ----------
Uchitel, O.D., Inchauspe, C.G., Urbano, F.J. & Di Guilmi, M.N. (2012) . Ca V2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis. Journal of Physiology Paris, 106(1-2), 12-22.
http://dx.doi.org/10.1016/j.jphysparis.2011.10.004
---------- CHICAGO ----------
Uchitel, O.D., Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N. "Ca V2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis" . Journal of Physiology Paris 106, no. 1-2 (2012) : 12-22.
http://dx.doi.org/10.1016/j.jphysparis.2011.10.004
---------- MLA ----------
Uchitel, O.D., Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N. "Ca V2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis" . Journal of Physiology Paris, vol. 106, no. 1-2, 2012, pp. 12-22.
http://dx.doi.org/10.1016/j.jphysparis.2011.10.004
---------- VANCOUVER ----------
Uchitel, O.D., Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N. Ca V2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis. J. Physiol. Paris. 2012;106(1-2):12-22.
http://dx.doi.org/10.1016/j.jphysparis.2011.10.004