Skip to main content
Fig. 2 | The Journal of Headache and Pain

Fig. 2

From: Migraine headache: a review of the molecular genetics of a common disorder

Fig. 2

Possible consequences of migraine mutations affecting the central glutamate synapse. Increased Ca2+ influx caused by mutations in familial hemiplegic migraine subtype 1 (FHM1) encoding Cav2.1 channels enhance glutamate release from presynaptic terminals. Loss of Na+/K+ ATPase function, occurring in FHM2, also reduces astrocyte uptake of glutamate leading to increased levels of the neurotransmitter in the synaptic cleft. The mutations in FHM3 can reduce firing of inhibitory interneurons or potentiate presynaptic action potential generation. Mutations in FHM5/SLC4A4 might inhibit glia-mediated acid secretion and thus free N-methyl-d-aspartate (NMDA) receptors from proton-mediated inhibition. Activity of EAAT1, the major glutamate transporter in the brain encoded by FHM6/SLC1A3, is directly affected by a mutation in its sequence and indirectly by a reported mutation in rs1835740, a variant located between MTDH and PGCP which might be up-regulated). The LRP1 gene has a role in glutamate signalling and the consequence of a reported mutation in rs11172113 might directly modulate NMDA-dependent calcium currents in vitro

Back to article page