File(s) under permanent embargo
Reason: This item is currently closed access.
Presynaptic Ca[subscript v]2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held
journal contribution
posted on 2014-09-25, 08:53 authored by Carlota Gonzalez Inchauspe, Francisco J. Urbano, Mariano N. Di Guilmi, Michel D. Ferrari, Arn M. J. M. van den Maagdenberg, Ian D. Forsythe, Osvaldo D. UchitelCa[subscript V]2.1 Ca[superscript 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[subscript 1A] pore-forming subunit of Ca[subscript 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[superscript 2+] concentration, we observed that with low Ca[superscript 2+] concentrations (<1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild type (WT), meaning significant differences in the nonlinear calcium dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K[superscript +] channels) via Ca[subscript v]2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short-term depression of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles.
History
Citation
Journal of Neurophysiology, 2012, 108 (11), pp. 2967-2976Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and PharmacologyPublished in
Journal of NeurophysiologyPublisher
American Physiological Societyissn
0022-3077eissn
1522-1598Copyright date
2014Publisher DOI
Publisher version
http://jn.physiology.org/content/108/11/2967Notes
Full text of this item is not currently available on the LRA. The final published version may be available through the links above.Language
enAdministrator link
Usage metrics
Categories
Keywords
Science & TechnologyLife Sciences & BiomedicineNeurosciencesPhysiologyNeurosciences & NeurologyNEUROSCIENCESPHYSIOLOGYR192Q knock-in micefamilial hemiplegic migraineCa(v)2.1 channelsexcitatory postsynaptic currentsshort-term synaptic plasticityCORTICAL SPREADING DEPRESSIONTRANSMITTER RELEASE RATESSHORT-TERM PLASTICITYFUNCTIONAL CONSEQUENCESPYRAMIDAL NEURONSK+ CHANNELSTRANSMISSIONVESICLESMICEINACTIVATION
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC