Top ▲
Gene and Protein Information ![]() |
|||||||
Species | TM | P Loops | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 24 | 0 | 2506 | 19p13.13 | CACNA1A | calcium voltage-gated channel subunit alpha1 A | |
Mouse | 24 | 0 | 2368 | 8 40.95 cM | Cacna1a | calcium channel, voltage-dependent, P/Q type, alpha 1A subunit | |
Rat | 24 | 0 | 2212 | 19q11 | Cacna1a | calcium voltage-gated channel subunit alpha1 A |
Previous and Unofficial Names ![]() |
α1A | APCA | CACNL1A4 | FHM | HPCA | MHP1 | BccA1 | brain calcium channel 1 | RBA-I | alpha1A | Ccha1a | SCA6 | calcium channel |
Database Links ![]() |
|
Alphafold | O00555 (Hs), P97445 (Mm), P54282 (Rn) |
ChEMBL Target | CHEMBL4266 (Hs) |
DrugBank Target | O00555 (Hs) |
Ensembl Gene | ENSG00000141837 (Hs), ENSMUSG00000034656 (Mm), ENSRNOG00000052707 (Rn) |
Entrez Gene | 773 (Hs), 12286 (Mm), 25398 (Rn) |
Human Protein Atlas | ENSG00000141837 (Hs) |
KEGG Gene | hsa:773 (Hs), mmu:12286 (Mm), rno:25398 (Rn) |
OMIM | 601011 (Hs) |
Orphanet | ORPHA119129 (Hs) |
Pharos | O00555 (Hs) |
RefSeq Nucleotide | NM_023035 (Hs), NM_000068 (Hs), NM_007578 (Mm), NM_012918 (Rn) |
RefSeq Protein | NP_000059 (Hs), NP_075461 (Hs), NP_031604 (Mm), NP_037050 (Rn) |
UniProtKB | O00555 (Hs), P97445 (Mm), P54282 (Rn) |
Wikipedia | CACNA1A (Hs) |
Associated Proteins ![]() |
||||||||||||||||||||||||||||||
|
|
|
||||||||||||||||||||||||||||
Associated Protein Comments | ||||||||||||||||||||||||||||||
Cav2.1 are regulated by a large signaling complex, including calmodulin, calmodulin-like calcium binding proteins, SNARE proteins, calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (reviewed in [7]). |
Functional Characteristics ![]() |
|
P/Q-type calcium current: High voltage-activated, moderate voltage-dependent inactivation |
Ion Selectivity and Conductance ![]() |
||||||
|
||||||
|
||||||
|
||||||
Ion Selectivity and Conductance Comments | ||||||
Murine channels in cerebellar Purkinje cells were found to have 3 distinct conductance levels at 9, 14 and 17pS [17]. |
Voltage Dependence ![]() |
||||||||||||||||
|
||||||||||||||||
|
||||||||||||||||
|
||||||||||||||||
Voltage Dependence Comments | ||||||||||||||||
The rates of Cav2.1 inactivation and V0.5,inact are differentially affected by co-expression with β1, β2, β3 and β4 subunits, as well as by alternative splicing of Cav2.1. Whole cell currents with slow P-type kinetics appear to be conducted by splice variants co-expressed with the β2 subunit. Whole cell currents with Q-type kinetics depend on an alternative splice in the domain I-II-linker [7,69,95]. |
Download all structure-activity data for this target as a CSV file
Gating inhibitors ![]() |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gating Inhibitor Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Alternative splicing of Cav2.1 alters sensitivity to ω-agatoxin IVA. Whole cell currents with Q-type pharmacology appear encoded by Cav splice variants containing Asp-Pro residues in the domain IV S3-S4 linker, while whole cell currents with P-type pharmacology appear encoded by Cav splice variants missing Asp-Pro residues in residues in domain IV S3-S4 linker. ω-agatoxin IVA exhibits ~10-fold difference in IC50 between P-type and Q-type channels [7]. ω-grammotoxin SIA causes a +110mV shift in the voltage dependence of Cav2.1 channels [66]. Notable Cav splice variants with physiological and/or pharmacological differences are found in refs [7,12,83,90,102]. |
Channel Blockers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
View species-specific channel blocker tables | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Channel Blocker Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
For further information and data on the role of ω-conotoxin MVIIC as a channel blocker of Cav2.1 see the following references: [7,32,67,95]. In addition, there exist a large number of non-specific small organic blockers of native and exogenously expressed P/Q-type currents [76]. |
Tissue Distribution ![]() |
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
Functional Assays ![]() |
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
||||||||||
|
Physiological Functions ![]() |
||||||||
|
||||||||
|
||||||||
|
||||||||
|
Physiological Consequences of Altering Gene Expression ![]() |
||||||||||
|
Phenotypes, Alleles and Disease Models ![]() |
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Clinically-Relevant Mutations and Pathophysiology ![]() |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
FHM-1, EA-2 and SCA6 are all autosomal dominant disorders [4] |
1. Adams ME, Mintz IM, Reily MD, Thanabal V, Bean BP. (1993) Structure and properties of omega-agatoxin IVB, a new antagonist of P-type calcium channels. Mol Pharmacol, 44 (4): 681-8. [PMID:8232218]
2. Adams PJ, Garcia E, David LS, Mulatz KJ, Spacey SD, Snutch TP. (2009) Ca(V)2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: implications for calcium channelopathies. Channels (Austin), 3 (2): 110-21. [PMID:19242091]
3. Adams PJ, Rungta RL, Garcia E, van den Maagdenberg AM, MacVicar BA, Snutch TP. (2010) Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel. Proc Natl Acad Sci USA, 107 (43): 18694-9. [PMID:20937883]
4. Adams PJ, Snutch TP. (2007) Calcium channelopathies: voltage-gated calcium channels. Subcell Biochem, 45: 215-51. [PMID:18193639]
5. Andreasen D, Friis UG, Uhrenholt TR, Jensen BL, Skøtt O, Hansen PB. (2006) Coexpression of voltage-dependent calcium channels Cav1.2, 2.1a, and 2.1b in vascular myocytes. Hypertension, 47 (4): 735-41. [PMID:16505211]
6. Barrett CF, Cao YQ, Tsien RW. (2005) Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. J Biol Chem, 280 (25): 24064-71. [PMID:15795222]
7. Bourinet E, Soong TW, Sutton K, Slaymaker S, Mathews E, Monteil A, Zamponi GW, Nargeot J, Snutch TP. (1999) Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels. Nat Neurosci, 2 (5): 407-15. [PMID:10321243]
8. Bowersox SS, Miljanich GP, Sugiura Y, Li C, Nadasdi L, Hoffman BB, Ramachandran J, Ko CP. (1995) Differential blockade of voltage-sensitive calcium channels at the mouse neuromuscular junction by novel omega-conopeptides and omega-agatoxin-IVA. J Pharmacol Exp Ther, 273 (1): 248-56. [PMID:7714772]
9. Cao YQ, Tsien RW. (2005) Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. Proc Natl Acad Sci USA, 102 (7): 2590-5. [PMID:15699344]
10. Carrera P, Piatti M, Stenirri S, Grimaldi LM, Marchioni E, Curcio M, Righetti PG, Ferrari M, Gelfi C. (1999) Genetic heterogeneity in Italian families with familial hemiplegic migraine. Neurology, 53 (1): 26-33. [PMID:10408532]
11. Cassola AC, Jaffe H, Fales HM, Afeche SC, Magnoli F, Cipolla-Neto J. (1998) ω-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer. Pflugers Arch, 436 (4): 545-52. [PMID:9683727]
12. Chaudhuri D, Chang SY, DeMaria CD, Alvania RS, Soong TW, Yue DT. (2004) Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels. J Neurosci, 24 (28): 6334-42. [PMID:15254089]
13. Chen WC, Xue HZ, Hsu YL, Liu Q, Patel S, Davis RL. (2011) Complex distribution patterns of voltage-gated calcium channel α-subunits in the spiral ganglion. Hear Res, 278 (1-2): 52-68. [PMID:21281707]
14. Day NC, Shaw PJ, McCormack AL, Craig PJ, Smith W, Beattie R, Williams TL, Ellis SB, Ince PG, Harpold MM et al.. (1996) Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus. Neuroscience, 71 (4): 1013-24. [PMID:8684604]
15. de Vries B, Stam AH, Beker F, van den Maagdenberg AM, Vanmolkot KR, Laan L, Ginjaar IB, Frants RR, Lauffer H, Haan J et al.. (2008) CACNA1A mutation linking hemiplegic migraine and alternating hemiplegia of childhood. Cephalalgia, 28 (8): 887-91. [PMID:18498393]
16. Denier C, Ducros A, Vahedi K, Joutel A, Thierry P, Ritz A, Castelnovo G, Deonna T, Gérard P, Devoize JL et al.. (1999) High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2. Neurology, 52 (9): 1816-21. [PMID:10371528]
17. Dove LS, Abbott LC, Griffith WH. (1998) Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice. J Neurosci, 18 (19): 7687-99. [PMID:9742139]
18. Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, Darcel F, Vicaut E, Bousser MG, Tournier-Lasserve E. (2001) The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med, 345 (1): 17-24. [PMID:11439943]
19. Ducros A, Denier C, Joutel A, Vahedi K, Michel A, Darcel F, Madigand M, Guerouaou D, Tison F, Julien J et al.. (1999) Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia. Am J Hum Genet, 64 (1): 89-98. [PMID:9915947]
20. Epi4K Consortium. (2016) De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. Am J Hum Genet, 99 (2): 287-98. [PMID:27476654]
21. Epi4K Consortium, Epilepsy Phenome/Genome Project, Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T et al.. (2013) De novo mutations in epileptic encephalopathies. Nature, 501 (7466): 217-21. [PMID:23934111]
22. Friend KL, Crimmins D, Phan TG, Sue CM, Colley A, Fung VS, Morris JG, Sutherland GR, Richards RI. (1999) Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM. Hum Genet, 105 (3): 261-5. [PMID:10987655]
23. Gardner K, BernalO, Keegan M, Badger J, Gerber O, Lowry N, Hoffman EP. (1999) A new mutation in the Chr19p calcium channel gene CACNLIA4 causing hemiplegic migraine with ataxia. Neurology, 52 (suppl. 2): A115.
24. Giffin NJ, Benton S, Goadsby PJ. (2002) Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A mutation. Dev Med Child Neurol, 44 (7): 490-3. [PMID:12162387]
25. Graves TD, Imbrici P, Kors EE, Terwindt GM, Eunson LH, Frants RR, Haan J, Ferrari MD, Goadsby PJ, Hanna MG et al.. (2008) Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2. Neurobiol Dis, 32 (1): 10-5. [PMID:18606230]
26. Guida S, Trettel F, Pagnutti S, Mantuano E, Tottene A, Veneziano L, Fellin T, Spadaro M, Stauderman K, Williams M et al.. (2001) Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2. Am J Hum Genet, 68 (3): 759-64. [PMID:11179022]
27. Gundlfinger A, Bischofberger J, Johenning FW, Torvinen M, Schmitz D, Breustedt J. (2007) Adenosine modulates transmission at the hippocampal mossy fibre synapse via direct inhibition of presynaptic calcium channels. J Physiol (Lond.), 582 (Pt 1): 263-77. [PMID:17478533]
28. Hans M, Luvisetto S, Williams ME, Spagnolo M, Urrutia A, Tottene A, Brust PF, Johnson EC, Harpold MM, Stauderman KA et al.. (1999) Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. J Neurosci, 19 (5): 1610-9. [PMID:10024348]
29. Hans M, Urrutia A, Deal C, Brust PF, Stauderman K, Ellis SB, Harpold MM, Johnson EC, Williams ME. (1999) Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels. Biophys J, 76 (3): 1384-400. [PMID:10049321]
30. Hansen PB, Jensen BL, Andreasen D, Friis UG, Skøtt O. (2000) Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles. Circ Res, 87 (10): 896-902. [PMID:11073885]
31. Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL et al.. (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Nature, 489 (7416): 391-9. [PMID:22996553]
32. Hillyard DR, Monje VD, Mintz IM, Bean BP, Nadasdi L, Ramachandran J, Miljanich G, Azimi-Zoonooz A, McIntosh JM, Cruz LJ. (1992) A new Conus peptide ligand for mammalian presynaptic Ca2+ channels. Neuron, 9 (1): 69-77. [PMID:1352986]
33. Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R, Kullmann DM, Hanna MG. (2004) Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain, 127 (Pt 12): 2682-92. [PMID:15483044]
34. Ishikawa K, Fujigasaki H, Saegusa H, Ohwada K, Fujita T, Iwamoto H, Komatsuzaki Y, Toru S, Toriyama H, Watanabe M et al.. (1999) Abundant expression and cytoplasmic aggregations of [alpha]1A voltage-dependent calcium channel protein associated with neurodegeneration in spinocerebellar ataxia type 6. Hum Mol Genet, 8 (7): 1185-93. [PMID:10369863]
35. Jen J, Kim GW, Baloh RW. (2004) Clinical spectrum of episodic ataxia type 2. Neurology, 62 (1): 17-22. [PMID:14718690]
36. Jen J, Wan J, Graves M, Yu H, Mock AF, Coulin CJ, Kim G, Yue Q, Papazian DM, Baloh RW. (2001) Loss-of-function EA2 mutations are associated with impaired neuromuscular transmission. Neurology, 57 (10): 1843-8. [PMID:11723274]
37. Jen J, Yue Q, Nelson SF, Yu H, Litt M, Nutt J, Baloh RW. (1999) A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia. Neurology, 53 (1): 34-7. [PMID:10408533]
38. Jeng CJ, Chen YT, Chen YW, Tang CY. (2006) Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated with episodic ataxia type 2. Am J Physiol, Cell Physiol, 290 (4): C1209-20. [PMID:16306128]
39. Jiménez C, Bourinet E, Leuranguer V, Richard S, Snutch TP, Nargeot J. (2000) Determinants of voltage-dependent inactivation affect Mibefradil block of calcium channels. Neuropharmacology, 39 (1): 1-10. [PMID:10665814]
40. Jouvenceau A, Eunson LH, Spauschus A, Ramesh V, Zuberi SM, Kullmann DM, Hanna MG. (2001) Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet, 358 (9284): 801-7. [PMID:11564488]
41. Kaeser PS, Deng L, Wang Y, Dulubova I, Liu X, Rizo J, Südhof TC. (2011) RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction. Cell, 144 (2): 282-95. [PMID:21241895]
42. Kaja S, van de Ven RC, Broos LA, Veldman H, van Dijk JG, Verschuuren JJ, Frants RR, Ferrari MD, van den Maagdenberg AM, Plomp JJ. (2005) Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness. Neuroscience, 135 (1): 81-95. [PMID:16111830]
43. Kipfer S, Jung S, Lemke JR, Kipfer-Kauer A, Howell JP, Kaelin-Lang A, Nyffeler T, Gutbrod K, Abicht A, Müri RM. (2013) Novel CACNA1A mutation(s) associated with slow saccade velocities. J Neurol, 260 (12): 3010-4. [PMID:24046065]
44. Kordasiewicz HB, Thompson RM, Clark HB, Gomez CM. (2006) C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity. Hum Mol Genet, 15 (10): 1587-99. [PMID:16595610]
45. Kors EE, Haan J, Giffin NJ, Pazdera L, Schnittger C, Lennox GG, Terwindt GM, Vermeulen FL, Van den Maagdenberg AM, Frants RR et al.. (2003) Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine. Arch Neurol, 60 (5): 684-8. [PMID:12756131]
46. Kors EE, Melberg A, Vanmolkot KR, Kumlien E, Haan J, Raininko R, Flink R, Ginjaar HB, Frants RR, Ferrari MD et al.. (2004) Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation. Neurology, 63 (6): 1136-7. [PMID:15452324]
47. Kors EE, Terwindt GM, Vermeulen FL, Fitzsimons RB, Jardine PE, Heywood P, Love S, van den Maagdenberg AM, Haan J, Frants RR et al.. (2001) Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol, 49 (6): 753-60. [PMID:11409427]
48. Kraus RL, Sinnegger MJ, Glossmann H, Hering S, Striessnig J. (1998) Familial hemiplegic migraine mutations change alpha1A Ca2+ channel kinetics. J Biol Chem, 273 (10): 5586-90. [PMID:9488686]
49. Kraus RL, Sinnegger MJ, Koschak A, Glossmann H, Stenirri S, Carrera P, Striessnig J. (2000) Three new familial hemiplegic migraine mutants affect P/Q-type Ca(2+) channel kinetics. J Biol Chem, 275 (13): 9239-43. [PMID:10734061]
50. Lampe RA, Defeo PA, Davison MD, Young J, Herman JL, Spreen RC, Horn MB, Mangano TJ, Keith RA. (1993) Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol Pharmacol, 44 (2): 451-60. [PMID:8394998]
51. Lee A, Westenbroek RE, Haeseleer F, Palczewski K, Scheuer T, Catterall WA. (2002) Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1. Nat Neurosci, 5 (3): 210-7. [PMID:11865310]
52. Lee A, Wong ST, Gallagher D, Li B, Storm DR, Scheuer T, Catterall WA. (1999) Ca2+/calmodulin binds to and modulates P/Q-type calcium channels. Nature, 399 (6732): 155-9. [PMID:10335845]
53. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ et al.. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature, 445 (7124): 168-76. [PMID:17151600]
54. Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, Luchian T, Adams DJ, Bond T, Thomas L et al.. (2000) Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem, 275 (45): 35335-44. [PMID:10938268]
55. Leão RM, Cruz JS, Diniz CR, Cordeiro MN, Beirão PS. (2000) Inhibition of neuronal high-voltage activated calcium channels by the omega-phoneutria nigriventer Tx3-3 peptide toxin. Neuropharmacology, 39 (10): 1756-67. [PMID:10884557]
56. Li L, Bischofberger J, Jonas P. (2007) Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons. J Neurosci, 27 (49): 13420-9. [PMID:18057200]
57. Liu H, De Waard M, Scott VE, Gurnett CA, Lennon VA, Campbell KP. (1996) Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2+ channel. J Biol Chem, 271 (23): 13804-10. [PMID:8662888]
58. Ludwig A, Flockerzi V, Hofmann F. (1997) Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain. J Neurosci, 17 (4): 1339-49. [PMID:9006977]
59. Luebke JI, Dunlap K, Turner TJ. (1993) Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron, 11 (5): 895-902. [PMID:7902110]
60. Magupalli VG, Mochida S, Yan J, Jiang X, Westenbroek RE, Nairn AC, Scheuer T, Catterall WA. (2013) Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2.1 calcium channels. J Biol Chem, 288 (7): 4637-48. [PMID:23255606]
61. Malmberg AB, Yaksh TL. (1994) Voltage-sensitive calcium channels in spinal nociceptive processing: blockade of N- and P-type channels inhibits formalin-induced nociception. J Neurosci, 14 (8): 4882-90. [PMID:8046458]
62. Mantuano E, Romano S, Veneziano L, Gellera C, Castellotti B, Caimi S, Testa D, Estienne M, Zorzi G, Bugiani M et al.. (2010) Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2. J Neurol Sci, 291 (1-2): 30-6. [PMID:20129625]
63. Mantuano E, Veneziano L, Spadaro M, Giunti P, Guida S, Leggio MG, Verriello L, Wood N, Jodice C, Frontali M. (2004) Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Ca(v)2.1 causing episodic ataxia 2. J Med Genet, 41 (6): e82. [PMID:15173248]
64. Matsuyama Z, Wakamori M, Mori Y, Kawakami H, Nakamura S, Imoto K. (1999) Direct alteration of the P/Q-type Ca2+ channel property by polyglutamine expansion in spinocerebellar ataxia 6. J Neurosci, 19 (12): RC14. [PMID:10366652]
65. McDonough SI, Boland LM, Mintz IM, Bean BP. (2002) Interactions among toxins that inhibit N-type and P-type calcium channels. J Gen Physiol, 119 (4): 313-28. [PMID:11929883]
66. McDonough SI, Lampe RA, Keith RA, Bean BP. (1997) Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA. Mol Pharmacol, 52 (6): 1095-104. [PMID:9415720]
67. McDonough SI, Swartz KJ, Mintz IM, Boland LM, Bean BP. (1996) Inhibition of calcium channels in rat central and peripheral neurons by omega-conotoxin MVIIC. J Neurosci, 16 (8): 2612-23. [PMID:8786437]
68. Melliti K, Grabner M, Seabrook GR. (2003) The familial hemiplegic migraine mutation R192Q reduces G-protein-mediated inhibition of P/Q-type (Ca(V)2.1) calcium channels expressed in human embryonic kidney cells. J Physiol (Lond.), 546 (Pt 2): 337-47. [PMID:12527722]
69. Mermelstein PG, Foehring RC, Tkatch T, Song WJ, Baranauskas G, Surmeier DJ. (1999) Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression. J Neurosci, 19 (17): 7268-77. [PMID:10460233]
70. Mintz IM. (1994) Block of Ca channels in rat central neurons by the spider toxin omega-Aga-IIIA. J Neurosci, 14 (5 Pt 1): 2844-53. [PMID:8182443]
71. Mintz IM, Adams ME, Bean BP. (1992) P-type calcium channels in rat central and peripheral neurons. Neuron, 9 (1): 85-95. [PMID:1321648]
72. Mintz IM, Sabatini BL, Regehr WG. (1995) Calcium control of transmitter release at a cerebellar synapse. Neuron, 15 (3): 675-88. [PMID:7546746]
73. Mintz IM, Venema VJ, Swiderek KM, Lee TD, Bean BP, Adams ME. (1992) P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature, 355 (6363): 827-9. [PMID:1311418]
74. Mochida S, Few AP, Scheuer T, Catterall WA. (2008) Regulation of presynaptic Ca(V)2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity. Neuron, 57 (2): 210-6. [PMID:18215619]
75. Müllner C, Broos LA, van den Maagdenberg AM, Striessnig J. (2004) Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects. J Biol Chem, 279 (50): 51844-50. [PMID:15448138]
76. Nimmrich V, Gross G. (2012) P/Q-type calcium channel modulators. Br J Pharmacol, 167 (4): 741-59. [PMID:22670568]
77. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M et al.. (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell, 87 (3): 543-52. [PMID:8898206]
78. Randall A, Tsien RW. (1995) Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons. J Neurosci, 15 (4): 2995-3012. [PMID:7722641]
79. Regan LJ, Sah DW, Bean BP. (1991) Ca2+ channels in rat central and peripheral neurons: high-threshold current resistant to dihydropyridine blockers and omega-conotoxin. Neuron, 6 (2): 269-80. [PMID:1847065]
80. Regehr WG, Mintz IM. (1994) Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Neuron, 12 (3): 605-13. [PMID:8155322]
81. Restituito S, Thompson RM, Eliet J, Raike RS, Riedl M, Charnet P, Gomez CM. (2000) The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunit-specific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. J Neurosci, 20 (17): 6394-403. [PMID:10964945]
82. Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA. (1996) Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25. Proc Natl Acad Sci U S A, 93 (14): 7363-8. [PMID:8692999]
83. Richards KS, Swensen AM, Lipscombe D, Bommert K. (2007) Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current. Eur J Neurosci, 26 (10): 2950-61. [PMID:18001290]
84. Romaniello R, Zucca C, Tonelli A, Bonato S, Baschirotto C, Zanotta N, Epifanio R, Righini A, Bresolin N, Bassi MT et al.. (2010) A wide spectrum of clinical, neurophysiological and neuroradiological abnormalities in a family with a novel CACNA1A mutation. J Neurol Neurosurg Psychiatr, 81 (8): 840-3. [PMID:20682717]
85. Roubertie A, Echenne B, Leydet J, Soete S, Krams B, Rivier F, Riant F, Tournier-Lasserve E. (2008) Benign paroxysmal tonic upgaze, benign paroxysmal torticollis, episodic ataxia and CACNA1A mutation in a family. J Neurol, 255 (10): 1600-2. [PMID:18758887]
86. Sidach SS, Mintz IM. (2002) Kurtoxin, a gating modifier of neuronal high- and low-threshold ca channels. J Neurosci, 22 (6): 2023-34. [PMID:11896142]
87. Sluka KA. (1997) Blockade of calcium channels can prevent the onset of secondary hyperalgesia and allodynia induced by intradermal injection of capsaicin in rats. Pain, 71 (2): 157-64. [PMID:9211477]
88. Sluka KA. (1998) Blockade of N- and P/Q-type calcium channels reduces the secondary heat hyperalgesia induced by acute inflammation. J Pharmacol Exp Ther, 287 (1): 232-7. [PMID:9765342]
89. Snutch TP, Leonard JP, Gilbert MM, Lester HA, Davidson N. (1990) Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci USA, 87 (9): 3391-3395. [PMID:1692134]
90. Soong TW, DeMaria CD, Alvania RS, Zweifel LS, Liang MC, Mittman S, Agnew WS, Yue DT. (2002) Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation. J Neurosci, 22 (23): 10142-52. [PMID:12451115]
91. Spacey SD, Hildebrand ME, Materek LA, Bird TD, Snutch TP. (2004) Functional implications of a novel EA2 mutation in the P/Q-type calcium channel. Ann Neurol, 56 (2): 213-20. [PMID:15293273]
92. Spacey SD, Materek LA, Szczygielski BI, Bird TD. (2005) Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia. Arch Neurol, 62 (2): 314-6. [PMID:15710862]
93. Stam AH, Vanmolkot KR, Kremer HP, Gärtner J, Brown J, Leshinsky-Silver E, Gilad R, Kors EE, Frankhuizen WS, Ginjaar HB et al.. (2008) CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine. Clin Genet, 74 (5): 481-5. [PMID:18400034]
94. Starr TV, Prystay W, Snutch TP. (1991) Primary structure of a calcium channel that is highly expressed in the rat cerebellum. Proc Natl Acad Sci USA, 88 (13): 5621-5. [PMID:1648226]
95. Stea A, Tomlinson WJ, Soong TW, Bourinet E, Dubel SJ, Vincent SR, Snutch TP. (1994) Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels. Proc Natl Acad Sci USA, 91 (22): 10576-80. [PMID:7524096]
96. Sutton KG, Siok C, Stea A, Zamponi GW, Heck SD, Volkmann RA, Ahlijanian MK, Snutch TP. (1998) Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3. Mol Pharmacol, 54 (2): 407-18. [PMID:9687583]
97. Takahashi T, Momiyama A. (1993) Different types of calcium channels mediate central synaptic transmission. Nature, 366 (6451): 156-8. [PMID:7901765]
98. Tonelli A, D'Angelo MG, Salati R, Villa L, Germinasi C, Frattini T, Meola G, Turconi AC, Bresolin N, Bassi MT. (2006) Early onset, non fluctuating spinocerebellar ataxia and a novel missense mutation in CACNA1A gene. J Neurol Sci, 241 (1-2): 13-7. [PMID:16325861]
99. Toru S, Murakoshi T, Ishikawa K, Saegusa H, Fujigasaki H, Uchihara T, Nagayama S, Osanai M, Mizusawa H, Tanabe T. (2000) Spinocerebellar ataxia type 6 mutation alters P-type calcium channel function. J Biol Chem, 275 (15): 10893-8. [PMID:10753886]
100. Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, Pietrobon D. (2002) Familial hemiplegic migraine mutations increase Ca(2+) influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons. Proc Natl Acad Sci USA, 99 (20): 13284-9. [PMID:12235360]
101. Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AM, Pietrobon D. (2005) Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. J Biol Chem, 280 (18): 17678-86. [PMID:15743764]
102. Tsunemi T, Saegusa H, Ishikawa K, Nagayama S, Murakoshi T, Mizusawa H, Tanabe T. (2002) Novel Cav2.1 splice variants isolated from Purkinje cells do not generate P-type Ca2+ current. J Biol Chem, 277 (9): 7214-21. [PMID:11756409]
103. Turner TJ, Adams ME, Dunlap K. (1992) Calcium channels coupled to glutamate release identified by omega-Aga-IVA. Science, 258 (5080): 310-3. [PMID:1357749]
104. Turner TJ, Adams ME, Dunlap K. (1993) Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release. Proc Natl Acad Sci USA, 90 (20): 9518-22. [PMID:8415733]
105. Tzour A, Sosial E, Meir T, Canello T, Naveh-Many T, Gabizon R, Nussinovitch I. (2013) Multiple pathways for high voltage-activated ca(2+) influx in anterior pituitary lactotrophs and somatotrophs. J Neuroendocrinol, 25 (1): 76-86. [PMID:22882461]
106. Uchitel OD, Protti DA, Sanchez V, Cherksey BD, Sugimori M, Llinás R. (1992) P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci USA, 89 (8): 3330-3. [PMID:1348859]
107. Vahedi K, Denier C, Ducros A, Bousson V, Levy C, Chabriat H, Haguenau M, Tournier-Lasserve E, Bousser MG. (2000) CACNA1A gene de novo mutation causing hemiplegic migraine, coma, and cerebellar atrophy. Neurology, 55 (7): 1040-2. [PMID:11061267]
108. Valence S, Cochet E, Rougeot C, Garel C, Chantot-Bastaraud S, Lainey E, Afenjar A, Barthez MA, Bednarek N, Doummar D et al.. (2019) Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies. Genet Med, 21 (3): 553-563. [PMID:29997391]
109. van den Maagdenberg AM, Kors EE, Brunt ER, van Paesschen W, Pascual J, Ravine D, Keeling S, Vanmolkot KR, Vermeulen FL, Terwindt GM et al.. (2002) Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene. J Neurol, 249 (11): 1515-9. [PMID:12420090]
110. van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ et al.. (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron, 41 (5): 701-10. [PMID:15003170]
111. Vieira LB, Kushmerick C, Hildebrand ME, Garcia E, Stea A, Cordeiro MN, Richardson M, Gomez MV, Snutch TP. (2005) Inhibition of high voltage-activated calcium channels by spider toxin PnTx3-6. J Pharmacol Exp Ther, 314 (3): 1370-7. [PMID:15933156]
112. Vila-Pueyo M, Gené GG, Flotats-Bastardes M, Elorza X, Sintas C, Valverde MA, Cormand B, Fernández-Fernández JM, Macaya A. (2014) A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy. Eur J Paediatr Neurol, 18 (3): 430-3. [PMID:24445160]
113. Wan J, Khanna R, Sandusky M, Papazian DM, Jen JC, Baloh RW. (2005) CACNA1A mutations causing episodic and progressive ataxia alter channel trafficking and kinetics. Neurology, 64 (12): 2090-7. [PMID:15985579]
114. Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, Groschner K, Glossmann H, Kraus RL, Grabner M et al.. (2002) Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem, 277 (9): 6960-6. [PMID:11742003]
115. Westenbroek RE, Babcock DF. (1999) Discrete regional distributions suggest diverse functional roles of calcium channel alpha1 subunits in sperm. Dev Biol, 207 (2): 457-69. [PMID:10068476]
116. Westenbroek RE, Hoskins L, Catterall WA. (1998) Localization of Ca2+ channel subtypes on rat spinal motor neurons, interneurons, and nerve terminals. J Neurosci, 18 (16): 6319-30. [PMID:9698323]
117. Westenbroek RE, Sakurai T, Elliott EM, Hell JW, Starr TV, Snutch TP, Catterall WA. (1995) Immunochemical identification and subcellular distribution of the alpha 1A subunits of brain calcium channels. J Neurosci, 15 (10): 6403-18. [PMID:7472404]
118. Yue Q, Jen JC, Nelson SF, Baloh RW. (1997) Progressive ataxia due to a missense mutation in a calcium-channel gene. Am J Hum Genet, 61 (5): 1078-87. [PMID:9345107]
119. Zamponi GW, Bourinet E, Snutch TP. (1996) Nickel block of a family of neuronal calcium channels: subtype- and subunit-dependent action at multiple sites. J Membr Biol, 151 (1): 77-90. [PMID:8661496]
120. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O'Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N et al.. (2014) An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. J Neurosci, 34 (36): 11929-47. [PMID:25186741]