Mutant P/Q-type calcium channel electrophysiology and migraine.
The pathophysiological mechanisms of migraine are not yet very well understood. The gene CACNA1A, coding for the alpha 1A subunit of neuronal P/Q-type Ca2+ channels is mutated in the rare Mendelian inherited variant, familial hemiplegic migraine. This finding suggests a role for disturbed neuronal Ca2+ influx and/or homeostasis in the pathophysiology of migraine. It has stimulated in vitro electrophysiological investigations into the function of mutant human and mouse P/Q-type channels at cell bodies and synapses. A complex picture has emerged from this work, showing that different CACNA1A mutations lead to different effects on Ca2+ channel behavior and that synaptic transmission may become affected. We will review these studies and discuss the possible implications for the understanding of migraine pathophysiology.
Plomp
J J
JJ
Department of Neurology, Department of Physiology and Medical Pharmacology, Leiden University Medical Center, POB 9600, 2300 RC, Leiden, The Netherlands. j.j.plomp@lumc.nl
van den Maagdenberg
A M
AM
Molenaar
P C
PC
Frants
R R
RR
Ferrari
M D
MD
D000818:Animals; D020865:Calcium Channels, P-Type / Q000235:genetics* / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000235:genetics* / Q000502:physiology*; D004594:Electrophysiology; D006429:Hemiplegia / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D013569:Synapses / Q000502:physiology
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type