Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models
One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms,...
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2014
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paper:paper_18672450_v6_n1_p15_Uchitel2023-06-08T16:29:51Z Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models Cav2.1 (P/Q-Type) Ca2+ channels Cortical spreading depression (CSD) Familial hemiplegic migraine R192Q and S218L knock in mice Synaptic transmission calcium channel 2.1 unclassified drug voltage gated calcium channel ataxia CACNA1A gene mutation circadian rhythm familial hemiplegic migraine familial hemiplegic migraine type 1 gene mutation headache human migraine mouse nerve cell plasticity nonhuman priority journal review spreading cortical depression synaptic transmission One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological diseases. This review addresses the mutations underlying familial hemiplegic migraine (FHM) with particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca2+ channel FHM type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of Cav2.1 channels. FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an increased open probability. These biophysical alterations may lead to a gain-of-function on synaptic transmission depending upon factors such as action potential waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM knock-in mouse models has demonstrated a deficient regulation of the cortical excitation/inhibition (E/I) balance. The resulting excessive increases in cortical excitation may be the mechanisms that underlie abnormal sensory processing together with an increase in the susceptibility to cortical spreading depression (CSD). Increasing evidence from FHM KI animal studies support the idea that CSD, the underlying mechanism of aura, can activate trigeminal nociception, and thus trigger the headache mechanisms. © 2013 International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18672450_v6_n1_p15_Uchitel http://hdl.handle.net/20.500.12110/paper_18672450_v6_n1_p15_Uchitel |
| 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 (P/Q-Type) Ca2+ channels Cortical spreading depression (CSD) Familial hemiplegic migraine R192Q and S218L knock in mice Synaptic transmission calcium channel 2.1 unclassified drug voltage gated calcium channel ataxia CACNA1A gene mutation circadian rhythm familial hemiplegic migraine familial hemiplegic migraine type 1 gene mutation headache human migraine mouse nerve cell plasticity nonhuman priority journal review spreading cortical depression synaptic transmission |
| spellingShingle |
Cav2.1 (P/Q-Type) Ca2+ channels Cortical spreading depression (CSD) Familial hemiplegic migraine R192Q and S218L knock in mice Synaptic transmission calcium channel 2.1 unclassified drug voltage gated calcium channel ataxia CACNA1A gene mutation circadian rhythm familial hemiplegic migraine familial hemiplegic migraine type 1 gene mutation headache human migraine mouse nerve cell plasticity nonhuman priority journal review spreading cortical depression synaptic transmission Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| topic_facet |
Cav2.1 (P/Q-Type) Ca2+ channels Cortical spreading depression (CSD) Familial hemiplegic migraine R192Q and S218L knock in mice Synaptic transmission calcium channel 2.1 unclassified drug voltage gated calcium channel ataxia CACNA1A gene mutation circadian rhythm familial hemiplegic migraine familial hemiplegic migraine type 1 gene mutation headache human migraine mouse nerve cell plasticity nonhuman priority journal review spreading cortical depression synaptic transmission |
| description |
One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological diseases. This review addresses the mutations underlying familial hemiplegic migraine (FHM) with particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca2+ channel FHM type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of Cav2.1 channels. FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an increased open probability. These biophysical alterations may lead to a gain-of-function on synaptic transmission depending upon factors such as action potential waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM knock-in mouse models has demonstrated a deficient regulation of the cortical excitation/inhibition (E/I) balance. The resulting excessive increases in cortical excitation may be the mechanisms that underlie abnormal sensory processing together with an increase in the susceptibility to cortical spreading depression (CSD). Increasing evidence from FHM KI animal studies support the idea that CSD, the underlying mechanism of aura, can activate trigeminal nociception, and thus trigger the headache mechanisms. © 2013 International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag Berlin Heidelberg. |
| title |
Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| title_short |
Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| title_full |
Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| title_fullStr |
Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| title_full_unstemmed |
Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| title_sort |
calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18672450_v6_n1_p15_Uchitel http://hdl.handle.net/20.500.12110/paper_18672450_v6_n1_p15_Uchitel |
| _version_ |
1768544659002359808 |