| Annotated protein: | Voltage-dependent P/Q-type calcium channel subunit alpha-1A (Brain calcium channel I) (BI) (Calcium channel, L type, alpha-1 polypeptide isoform 4) (Voltage-gated calcium channel subunit alpha Cav2.1). Gene symbol: CACNA1A. Taxonomy: Mus musculus (Mouse). Uniprot ID: P97445 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CACNA1A |
| Ontology domain: | Biological Process |
| SynGO term: | voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels (GO:0099626) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Vecchia D, et al. "Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans" Front Cell Neurosci. 2015 Feb 17;9:8 PMID:25741235 |
| Figure(s): | Fig 1, Fig 2, Fig 3, Fig 4, Fig 5 |
| Annotation description: | This manuscript describes analysis of synaptic transmission in cortical neuronal autaptic cultures where a point mutation in a Cav2.1 (S218L) has been introduced by knock-in. The mutation is disease-related in humans and is strongly associated with migraine. This analysis shows that neurons in which harbor Cav2,1 with the S218L mutation clearly change presynaptic function. Neurons harboring this mutation show a greater susceptibility to block by the Cav2.1 blocker agatoxin, an increase in release probability and a shift in the Ca-dependence of of release to lower values. These changes were only seen in excitatory neurons, not inhibitory. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) none of the above |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp |
| Annotator(s): | Ryan J. Farrell (ORCID:0000-0003-4022-8707) Ghazaleh Ashrafi (ORCID:0000-0001-7480-0826) Camila Pulido (ORCID:0000-0002-5648-066X) Jaime de Juan-Sanz (ORCID:0000-0002-1212-5623) Timothy Ryan (ORCID:0000-0003-2533-9548) |
| Lab: | Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA |
| Additional literature: | This reference describes the identification of omega-Agatoxin-IVA as a blocker of P-type Calcium channels. The peptide toxin from funnel web spider venom blocked high threshold P-type Calcium currents in rat Purkinje neurons (Fig 3). with a low (6-200) nanomolar concentration blocking approximately 94% of the Calcium current. In DRG neurons omega-Agatoxin-GVIA blocked only 0-24% of the high threshold Calcium current. Block by saturating concentrations of omega-Agatoxin-GVIA did not prevent additional block of Calcium currents by omega-Conotoxin and nitrendipine. @ PMID:1311418 Provides evidence for the role of Q-type Calcium channels in supporting synaptic transmission between the hipocampal CA3 to CA1 neurons. Fig 1A, B show that omega-Conotoxin-GVIA, a specific blocker of N-type channels reduces but does not eliminate synaptic transmission. Synaptic transmission was unaffected by FPL 64176, an agonist of L-type channels or nimodipine, a specific blocker of L-type channels (Fig. 1C). Fig 1D shows that addition of omega-Agatoxin-IVA (a specific blocker of P-type Calcium channels) has no effect on synaptic transmission. However. removal of external Calcium causes a complete block in synaptic transmission (Fig 1D). Application of omega-Conotoxin-MVIIC (5 micromolar) which blocks both N and Q-type Calcium channels abolished synaptic transmission (Fig 1C). The effects of omega-Conotoxin-MVIIC were dose dependent and could be partially washed out (Fig 1C). @ PMID:7832825 |
| SynGO annotation ID: | 411 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |