[Role of P/Q calcium channel in familial hemiplegic migraine].
Voltage-dependent calcium channels constitute one of the main pathways of calcium entry into neurons. They are the principal actors of synaptic transmission by controlling the release of neurotransmitters. They also contribute to numerous other cell functions, such as gene expression or synaptogenesis. These channels, by their essential cell functions, are at the origin of numerous channelopathies resulting from mutations of the genes encoding their different subunits. Familial Hemiplegic Migraine (FHM) represents one such example of these channelopathies. In this human disease, genetic studies have demonstrated the implication of the CACNA1A gene in a type 1 form of FHM. This gene encodes for the Ca(v)2.1 subunit of P/Q calcium channels and is the target of numerous mutations affecting the properties of channel activity. The question on how discrete mutations of this gene are able to alter the activity of the channel and contribute to the physiopathology of FHM remains an open question. The functional characterization of mutated channels in various heterologous expression systems, as well as in vivo in an animal model, provides a molecular scheme of the physiopathology of FHM in which neurons, astrocytes and blood circulation act in concert.
Weiss
Norbert
N
Inserm U607, Laboratoire Canaux calciques, fonctions et pathologies, 17 rue des Martyrs, Bâtiment C3, 38054 Grenoble Cedex 09, France.
Tournier-Lasserve
Elisabeth
E
De Waard
Michel
M
D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D017124:Conserved Sequence; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type