Presynaptic CaV2.1 calcium channels carrying a familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held

GONZALEZ INCHAUSPE C; URBANO FJ; DI GUILMI M.; FERRARI M.D.; VAN DEN MAAGDENBERG, A. M.; FORSYTHE ID; UCHITEL O.D.

JOURNAL OF NEUROPHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Lugar: Bethesda; Año: 2012 vol. 108 p. 2967 - 2976

0022-3077

Ca(V)2.1 Ca(2+) channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α(1A) pore-forming subunit of Ca(V)2.1 channel. We used knock-in (KI) transgenic mice harboring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the medial nucleus of the trapezoid body (MNTB). Although synaptic transmission seems unaffected by low-frequency stimulation in physiological Ca(2+) concentration, we observed that with low Ca(2+) concentrations (