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Inchauspe, C.G.; Urbano, F.J.; Di Guilmi, M.N.; Forsythe, I.D.; Ferrari, M.D.; Van Den Maagdenberg, A.M.J.M.; Uchitel, O.D. "Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential" (2010) Journal of Neurophysiology. 104(1):291-299
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Abstract:

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 Ca2+ 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). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI CaV2.1 Ca2+ channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (IpCa) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. CaV2.1 Ca2+ channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca2+ currents (I Ca) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when ICa was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca2+ currents evoked at the presynaptic terminals (IpCa)of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine. Copyright © 2010 The American Physiological Society.

Registro:

Documento: Artículo
Título:Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential
Autor:Inchauspe, C.G.; Urbano, F.J.; Di Guilmi, M.N.; Forsythe, I.D.; Ferrari, M.D.; Van Den Maagdenberg, A.M.J.M.; Uchitel, O.D.
Filiación:Inst. de Fisiología, Biología Molecular Y Neurociencias (LFBM-IFIBYNE), UBA, CONICET, Intendente Guiraldes 2670, C1428BGA Buenos Aires, Argentina
Neurotoxicity at the Synaptic Interface, Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom
Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands
Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands
Palabras clave:calcium channel; calcium ion; action potential; article; calcium current; controlled study; excitatory postsynaptic potential; familial hemiplegic migraine; gene mutation; missense mutation; mouse; neurotransmission; neurotransmitter release; nonhuman; patch clamp; priority journal; pyramidal nerve cell; synapse; synaptic transmission; synaptosome; transgenic mouse; whole cell; Action Potentials; Animals; Calcium Channels; Cerebral Cortex; Electric Stimulation; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Migraine Disorders; Migraine with Aura; Neurons, Afferent; Neurotransmitter Agents; Patch-Clamp Techniques; Pyramidal Cells; Synapses; Synaptic Transmission
Año:2010
Volumen:104
Número:1
Página de inicio:291
Página de fin:299
DOI: http://dx.doi.org/10.1152/jn.00034.2010
Título revista:Journal of Neurophysiology
Título revista abreviado:J. Neurophysiol.
ISSN:00223077
CODEN:JONEA
CAS:calcium ion, 14127-61-8; CACNA1A protein, human; Calcium Channels; Neurotransmitter Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223077_v104_n1_p291_Inchauspe

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Citas:

---------- APA ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Forsythe, I.D., Ferrari, M.D., Van Den Maagdenberg, A.M.J.M. & Uchitel, O.D. (2010) . Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential. Journal of Neurophysiology, 104(1), 291-299.
http://dx.doi.org/10.1152/jn.00034.2010
---------- CHICAGO ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Forsythe, I.D., Ferrari, M.D., Van Den Maagdenberg, A.M.J.M., et al. "Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential" . Journal of Neurophysiology 104, no. 1 (2010) : 291-299.
http://dx.doi.org/10.1152/jn.00034.2010
---------- MLA ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Forsythe, I.D., Ferrari, M.D., Van Den Maagdenberg, A.M.J.M., et al. "Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential" . Journal of Neurophysiology, vol. 104, no. 1, 2010, pp. 291-299.
http://dx.doi.org/10.1152/jn.00034.2010
---------- VANCOUVER ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Forsythe, I.D., Ferrari, M.D., Van Den Maagdenberg, A.M.J.M., et al. Gain of function in FHM-1 CaV2.1 knock-in mice is related to the shape of the action potential. J. Neurophysiol. 2010;104(1):291-299.
http://dx.doi.org/10.1152/jn.00034.2010