INVESTIGADORES
UCHITEL Osvaldo Daniel
artículos
Título:
CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis.
Autor/es:
UCHITEL OD.; INCHAUSPE CG; URBANO FJ; DI GUILMI MN
Revista:
JOURNAL OF PHYSIOLOGY (PARIS)
Editorial:
ELSEVIER SCI LTD
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 106 p. 12 - 22
ISSN:
0928-4257
Resumen:
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 CaV2.1 (i.e., P/Q-type)
voltage-activated Ca2+ 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 CaV2.1 channels. Mutated CaV2.1 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.