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Calcium channels of the P/Q subtype mediate transmitter release at the neuromuscular junction and at many central synapses, such as the calyx of Held. Transgenic mice in which alpha1A channels are ablated provide a powerful tool with which to test compensatory mechanisms at the synapse and to explore mechanisms of presynaptic regulation associated with(More)
22 23 Familial hemiplegic migraine type-1 (FHM1) is caused by missense mutations in the CACNA1A 24 gene that encodes the α 1A pore-forming subunit of Ca V 2.1 Ca 2+ channels. We used knock-in (KI) 25 transgenic mice harbouring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the 26 calyx of Held synapse and cortical layer 2/3 pyramidal(More)
P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmitting central synapses, but the reasons for the specific expression of one or the other in each particular synapse are not known. Using whole-cell patch clamping from in vitro slices of the auditory brainstem we have examined presynaptic calcium currents (I(pCa)) and(More)
Specific missense mutations in the CACNA1A gene, which encodes a subunit of voltage-gated CaV2.1 channels, are associated with familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of common migraine with aura. We used transgenic knock-in (KI) mice harboring the human pathogenic FHM1 mutation S218L to study presynaptic Ca(2+) currents, EPSCs,(More)
Studies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. In this review we focus on the role of mutated CaV2.1 (i.e., P/Q-type) voltage-activated Ca2+ channels, and on the(More)
Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the alpha(1A) pore-forming subunit of Ca(V)2.1 Ca(2+) channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs).(More)
den Maagdenberg provide the genetically modified 33 R192Q KI mice. Abstract 36 Ca V 2.1 Ca 2+ channels have a dominant and specific role in initiating fast synaptic transmission at 37 central excitatory synapses, through a close association between release sites and calcium sensors. 38 Familial hemiplegic migraine type-1 (FHM-1) is an autosomal-dominant(More)
In this work, we studied the effects of the anticonvulsant and analgesic drug pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons of the mouse medial nucleus of the trapezoid body and on presynaptic calcium currents at the calyx of Held. We found that the acute application of PGB reduced the amplitude of EPSCs in a(More)
CaV2.1 Ca(2+) channels play a key role in triggering neurotransmitter release and mediating synaptic transmission. Familial hemiplegic migraine type-1 (FHM-1) is caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 Ca(2+) channels. We used knock-in (KI) transgenic mice harbouring the pathogenic FHM-1 mutation(More)
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(More)