Referenced in: Cav2.1

Automatically associated channels: Cav2.1

Title: A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

Authors: Arn M J M Van Den Maagdenberg, Daniela Pietrobon, Tommaso Pizzorusso, Simon Kaja, Ludo A M Broos, Tiziana Cesetti, Rob C G Van De Ven, Angelita Tottene, Jos van der Kaa, Jaap J Plomp, Rune R Frants, Michel D Ferrari

Journal, date & volume: Neuron, 2004 Mar 4 , 41, 701-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15003170

Abstract
Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and found multiple gain-of-function effects. These include increased Ca(v)2.1 current density in cerebellar neurons, enhanced neurotransmission at the neuromuscular junction, and, in the intact animal, a reduced threshold and increased velocity of cortical spreading depression (CSD; the likely mechanism for the migraine aura). Our data show that the increased susceptibility for CSD and aura in migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a promising animal model to study migraine mechanisms and treatments.