Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held
CaV2.1 Ca2+ 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, c...
Guardado en:
| Autores principales: | , |
|---|---|
| Publicado: |
2012
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223077_v108_n11_p2967_Inchauspe http://hdl.handle.net/20.500.12110/paper_00223077_v108_n11_p2967_Inchauspe |
| Aporte de: |
| id |
paper:paper_00223077_v108_n11_p2967_Inchauspe |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_00223077_v108_n11_p2967_Inchauspe2023-06-08T14:49:11Z Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel Cav2.1 channels Excitatory postsynaptic currents Familial hemiplegic migraine R192Q knock-in mice Short-term synaptic plasticity arginine calcium egtazic acid glutamine potassium channel unclassified drug voltage gated calcium channel voltage gated calcium channel 2.1 Cacna1a protein, mouse calcium channel P type calcium channel Q type chelating agent glutamic acid potassium channel blocking agent action potential animal cell animal tissue article calyx of Held excitatory postsynaptic potential exocytosis familial hemiplegic migraine gene mutation long term depression medial nucleus of the trapezoid body mouse nerve cell nerve fiber nerve stimulation neurotransmitter release nonhuman presynaptic nerve priority journal synapse vesicle synaptic transmission transgenic mouse wild type animal auditory nervous system cerebellar ataxia cytology excitatory postsynaptic potential genetics metabolism migraine missense mutation nerve cell plasticity physiology pons sensory nerve cell synaptosome Action Potentials Animals Auditory Pathways Calcium Calcium Channels, P-Type Calcium Channels, Q-Type Cerebellar Ataxia Chelating Agents Excitatory Postsynaptic Potentials Exocytosis Glutamic Acid Mice Mice, Transgenic Migraine Disorders Mutation, Missense Neuronal Plasticity Neurons, Afferent Pons Potassium Channel Blockers Presynaptic Terminals CaV2.1 Ca2+ 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 α1A pore-forming subunit of CaV2.1 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 Ca2+ concentration, we observed that with low Ca2+ 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+ channels) via Cav2.1-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. © 2012 the American Physiological Society. Fil:Di Guilmi, M.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uchitel, O.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223077_v108_n11_p2967_Inchauspe http://hdl.handle.net/20.500.12110/paper_00223077_v108_n11_p2967_Inchauspe |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cav2.1 channels Excitatory postsynaptic currents Familial hemiplegic migraine R192Q knock-in mice Short-term synaptic plasticity arginine calcium egtazic acid glutamine potassium channel unclassified drug voltage gated calcium channel voltage gated calcium channel 2.1 Cacna1a protein, mouse calcium channel P type calcium channel Q type chelating agent glutamic acid potassium channel blocking agent action potential animal cell animal tissue article calyx of Held excitatory postsynaptic potential exocytosis familial hemiplegic migraine gene mutation long term depression medial nucleus of the trapezoid body mouse nerve cell nerve fiber nerve stimulation neurotransmitter release nonhuman presynaptic nerve priority journal synapse vesicle synaptic transmission transgenic mouse wild type animal auditory nervous system cerebellar ataxia cytology excitatory postsynaptic potential genetics metabolism migraine missense mutation nerve cell plasticity physiology pons sensory nerve cell synaptosome Action Potentials Animals Auditory Pathways Calcium Calcium Channels, P-Type Calcium Channels, Q-Type Cerebellar Ataxia Chelating Agents Excitatory Postsynaptic Potentials Exocytosis Glutamic Acid Mice Mice, Transgenic Migraine Disorders Mutation, Missense Neuronal Plasticity Neurons, Afferent Pons Potassium Channel Blockers Presynaptic Terminals |
| spellingShingle |
Cav2.1 channels Excitatory postsynaptic currents Familial hemiplegic migraine R192Q knock-in mice Short-term synaptic plasticity arginine calcium egtazic acid glutamine potassium channel unclassified drug voltage gated calcium channel voltage gated calcium channel 2.1 Cacna1a protein, mouse calcium channel P type calcium channel Q type chelating agent glutamic acid potassium channel blocking agent action potential animal cell animal tissue article calyx of Held excitatory postsynaptic potential exocytosis familial hemiplegic migraine gene mutation long term depression medial nucleus of the trapezoid body mouse nerve cell nerve fiber nerve stimulation neurotransmitter release nonhuman presynaptic nerve priority journal synapse vesicle synaptic transmission transgenic mouse wild type animal auditory nervous system cerebellar ataxia cytology excitatory postsynaptic potential genetics metabolism migraine missense mutation nerve cell plasticity physiology pons sensory nerve cell synaptosome Action Potentials Animals Auditory Pathways Calcium Calcium Channels, P-Type Calcium Channels, Q-Type Cerebellar Ataxia Chelating Agents Excitatory Postsynaptic Potentials Exocytosis Glutamic Acid Mice Mice, Transgenic Migraine Disorders Mutation, Missense Neuronal Plasticity Neurons, Afferent Pons Potassium Channel Blockers Presynaptic Terminals Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| topic_facet |
Cav2.1 channels Excitatory postsynaptic currents Familial hemiplegic migraine R192Q knock-in mice Short-term synaptic plasticity arginine calcium egtazic acid glutamine potassium channel unclassified drug voltage gated calcium channel voltage gated calcium channel 2.1 Cacna1a protein, mouse calcium channel P type calcium channel Q type chelating agent glutamic acid potassium channel blocking agent action potential animal cell animal tissue article calyx of Held excitatory postsynaptic potential exocytosis familial hemiplegic migraine gene mutation long term depression medial nucleus of the trapezoid body mouse nerve cell nerve fiber nerve stimulation neurotransmitter release nonhuman presynaptic nerve priority journal synapse vesicle synaptic transmission transgenic mouse wild type animal auditory nervous system cerebellar ataxia cytology excitatory postsynaptic potential genetics metabolism migraine missense mutation nerve cell plasticity physiology pons sensory nerve cell synaptosome Action Potentials Animals Auditory Pathways Calcium Calcium Channels, P-Type Calcium Channels, Q-Type Cerebellar Ataxia Chelating Agents Excitatory Postsynaptic Potentials Exocytosis Glutamic Acid Mice Mice, Transgenic Migraine Disorders Mutation, Missense Neuronal Plasticity Neurons, Afferent Pons Potassium Channel Blockers Presynaptic Terminals |
| description |
CaV2.1 Ca2+ 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 α1A pore-forming subunit of CaV2.1 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 Ca2+ concentration, we observed that with low Ca2+ 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+ channels) via Cav2.1-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. © 2012 the American Physiological Society. |
| author |
Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel |
| author_facet |
Di Guilmi, Mariano Nicolas Uchitel, Osvaldo Daniel |
| author_sort |
Di Guilmi, Mariano Nicolas |
| title |
Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| title_short |
Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| title_full |
Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| title_fullStr |
Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| title_full_unstemmed |
Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held |
| title_sort |
presynaptic cav2.1 calcium channels carrying familial hemiplegic migraine mutation r192q allow faster recovery from synaptic depression in mouse calyx of held |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223077_v108_n11_p2967_Inchauspe http://hdl.handle.net/20.500.12110/paper_00223077_v108_n11_p2967_Inchauspe |
| work_keys_str_mv |
AT diguilmimarianonicolas presynapticcav21calciumchannelscarryingfamilialhemiplegicmigrainemutationr192qallowfasterrecoveryfromsynapticdepressioninmousecalyxofheld AT uchitelosvaldodaniel presynapticcav21calciumchannelscarryingfamilialhemiplegicmigrainemutationr192qallowfasterrecoveryfromsynapticdepressioninmousecalyxofheld |
| _version_ |
1768545681729912832 |