CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

UCHITEL OD; GONZALEZ INCHAUSPE C; URBANO FJ; DI GUILMI MN

JOURNAL OF PHYSIOLOGY (PARIS)

ELSEVIER SCI LTD

Lugar: Paris; Año: 2011 vol. 106 p. 12 - 22

0928-4257

AbstractStudies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ionchannels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeuticapproaches 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 mutationscausing familial hemiplegic migraine type-1 (FHM1) have in neurotransmitter release. Transgenicmice harbouring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used asmodels to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are apowerful 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 insynaptic transmission. This gain-of-function might underlie alterations in the excitatory/ inhibitorybalance of synaptic transmission, favoring a persistent state of hyperexcitability in cortical neurons thatwould increase the susceptibility for cortical spreading depression (CSD), a mechanism believed toinitiate the attacks of migraine with aura.