Deciphering migraine.
Migraine is an episodic headache disorder affecting as many as 10% of people worldwide. Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of severe migraine accompanied by visual disturbances known as aura. Migrainous aura is caused by cortical spreading depression (CSD) - a slowly advancing wave of tissue depolarization in the cortex. More than half of FHM cases are caused by mutations in the CACNA1A gene, which encodes a neuronal Cav2.1 Ca2+ channel, resulting in increased Ca2+ flow into dendrites and excessive release of the excitatory neurotransmitter glutamate. In this issue of the JCI, Eikermann-Haerter et al. show that transgenic mice with FHM-associated mutations in Cacna1a have increased susceptibility to CSD compared with wild-type animals, likely due to augmentation of excitatory neurotransmission (see the related article beginning on page 99). Additional as-yet-undefined channel mutations may similarly render the migraine brain more susceptible to the initiation of CSD, with implications not only for the genesis of migraine but also for the hypoxic injury that accompanies its worst manifestation, complicated migraine.
Takano
Takahiro
T
Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester, Rochester, New York 14642, USA.
Nedergaard
Maiken
M
D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D013181:Cortical Spreading Depression / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008881:Migraine Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D011188:Potassium; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type