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Trigeminal ganglion neuron subtype‐specific alterations of Ca V 2.1 calcium current and excitability in a Cacna1a mouse model of migraine
Author(s) -
Fioretti B.,
Catacuzzeno L.,
Sforna L.,
GerkeDuncan M. B.,
van den Maagdenberg A. M. J. M.,
Franciolini F.,
Connor M.,
Pietrobon D.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.220533
Subject(s) - meninges , trigeminal ganglion , familial hemiplegic migraine , calcitonin gene related peptide , migraine , calcium channel , neuroscience , trigeminal nerve , calcitonin , voltage dependent calcium channel , calcium , medicine , endocrinology , biology , chemistry , anatomy , neuropeptide , receptor , migraine with aura , aura , sensory system
Non‐technical summary Activation of trigeminal neurons innervating the meninges and release of proinflammatory peptides (in particular calcitonin gene‐related peptide (CGRP)) from their terminals are believed to play a key role in generating migraine pain. A monogenic subtype of migraine (familial hemiplegic migraine type‐1 (FHM1)) is caused by gain‐of‐function mutations in a neuronal voltage‐gated calcium channel (Ca v 2.1) involved in controlling neurotransmitter release from many synaptic terminals including those of trigeminal neurons at the meninges. Using a FHM1 transgenic mouse model, we show that the migraine mutation produces gain‐of‐function (i.e. it increases calcium influx) in a subpopulation of trigeminal neurons that do not innervate the meninges. In contrast, the calcium channels of trigeminal neurons innervating the meninges and releasing CGRP are not affected by the mutation. Congruently, the migraine mutation does not alter CGRP release at the meninges. Our findings suggest that the facilitation of CGRP actions at the meninges does not contribute to the generation of headache in FHM1.