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.