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Cav3.2

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Target id: 536

Nomenclature: Cav3.2

Family: Voltage-gated calcium channels (CaV)

Contents:

Gene and Protein Information Click here for help
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 1 2353 16p13.3 CACNA1H calcium voltage-gated channel subunit alpha1 H 10
Mouse 24 1 2365 17 12.53 cM Cacna1h calcium channel, voltage-dependent, T type, alpha 1H subunit 22
Rat 24 1 2359 10q12 Cacna1h calcium voltage-gated channel subunit alpha1 H 31
Previous and Unofficial Names Click here for help
a1H | alpha-1H | calcium channel
Database Links Click here for help
Alphafold O95180 (Hs), O88427 (Mm), Q9EQ60 (Rn)
ChEMBL Target CHEMBL1859 (Hs), CHEMBL3600280 (Mm), CHEMBL5134 (Rn)
DrugBank Target O95180 (Hs)
Ensembl Gene ENSG00000196557 (Hs), ENSMUSG00000024112 (Mm), ENSRNOG00000033893 (Rn)
Entrez Gene 8912 (Hs), 58226 (Mm), 114862 (Rn)
Human Protein Atlas ENSG00000196557 (Hs)
KEGG Gene hsa:8912 (Hs), mmu:58226 (Mm), rno:114862 (Rn)
OMIM 607904 (Hs)
Orphanet ORPHA286549 (Hs)
Pharos O95180 (Hs)
RefSeq Nucleotide NM_021098 (Hs), NM_021415 (Mm), NM_153814 (Rn)
RefSeq Protein NP_066921 (Hs), NP_067390 (Mm), NP_722521 (Rn)
UniProtKB O95180 (Hs), O88427 (Mm), Q9EQ60 (Rn)
Wikipedia CACNA1H (Hs)
Functional Characteristics Click here for help
T-type calcium current: Low voltage-activated, fast voltage-dependent inactivation
Ion Selectivity and Conductance Click here for help
Species:  Human
Rank order:  Ca2+ [9.1 pS] = Ba2+
References:  53
Species:  Rat
Rank order:  Sr2+ = Ba2+ = Ca2+
References:  40-42
Voltage Dependence Click here for help
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -47.4 2.0 – 7.0 33 Dorsal root ganglion nociceptive neurons. Rat
Inactivation  -70.8 25.0 – 75.0 33
Comments  Native currents, recorded in 10 BaCl2. Kinetics recorded during test pulses to -50 mV (high) and -10 mV (low).
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -59.9 – -51.8 (median: -55.9) 1.6 – 8.4 51 HEK 293 cells. Human
Inactivation  -86.5 – -81.7 (median: -84.8) 12.9 – 32.6 51
Comments  Recombinant, recorded in 5 mM CaCl2. The range of V0.5 values result from epilepsy mutations, while the kinetics reflects voltage dependence; the high values were recorded during test potentials to -55 mV; the low at -15 mV.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -43.7 1.8 – 9.9 15 HEK 293 cells. Human
Inactivation  -78.8 15.0 – 28.0 15
Comments  Recombinant, recorded in 5 mM CaCl2. The range of kinetics reflects voltage dependence: the high values recorded during test potentials to -50mV; the low to -10mV.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -44.0 – -38.6 (median: -41.9) 2.0 – 10.0 56 HEK 293 cells. Human
Inactivation  -56.6 – -46.9 (median: -50.7) 20.0 – 120.0 56
Comments  Recombinant, recorded in 2 mM CaCl2. Range of V0.5 values result from splice variation, while kinetics reflects voltage dependence: high recorded during test potentials to -50 mV; low at -15 mV. Values of V0.5,inact are more positive than other estimates due to the use of a short prepulse (0.2s vs. typical 5-15s).

Download all structure-activity data for this target as a CSV file go icon to follow link

Gating inhibitors Click here for help
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
kurtoxin Peptide Click here for species-specific activity table Rn Antagonist 7.3 – 7.6 pIC50 - -90.0 8,44
⤷ pIC50 7.3 – 7.6 (IC50 5.01x10-8 – 2.51x10-8 M) [8,44]
Holding voltage: -90.0 mV
Gating Inhibitor Comments
Kurtoxin was selective for recombinant channels expressed in oocytes, but not for native T-currents in thalamocortical cells [8,44].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
suvecaltamide Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 - - 36
⤷ pIC50 8.1 (IC50 8.2x10-9 M) [36]
TTA-A2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Pore blocker 8.0 pIC50 - -75.0 12
⤷ pIC50 8.0 [12]
Holding voltage: -75.0 mV
ACT-709478 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 - - 2
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [2]
pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Pore blocker 7.3 pIC50 - -100.0 37
⤷ pIC50 7.3 [37]
Holding voltage: -100.0 mV
TTA-P2 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Pore blocker 7.0 pIC50 - -90.0 6
⤷ pIC50 7.0 [6]
Holding voltage: -90.0 mV
and derivatives pimozide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Pore blocker 6.8 pIC50 - - 19
⤷ pIC50 6.8 [19]
Z944 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Pore blocker 6.8 pIC50 - -75.0 48
⤷ pIC50 6.8 voltage-dependent [48]
Holding voltage: -75.0 mV
mibefradil Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Pore blocker 5.9 – 7.2 pIC50 - -110.0 – -80.0 28
⤷ pIC50 5.9 – 7.2 (IC50 1.1x10-6 – 6.9x10-8 M) [28]
Holding voltage: -110.0 – -80.0 mV
anandamide Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Antagonist 6.5 pIC50 - -80.0 3
⤷ pIC50 6.5 [3]
Holding voltage: -80.0 mV
ML218 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Pore blocker 6.5 pIC50 - -90.0 54
⤷ pIC50 6.5 [54]
Holding voltage: -90.0 mV
efonidipine Small molecule or natural product Approved drug Hs Pore blocker 6.4 pIC50 - - 25
⤷ pIC50 6.4 [25]
ABT-639 Small molecule or natural product Click here for species-specific activity table Hs Pore blocker 5.6 pIC50 - -110.0 18
⤷ pIC50 5.6 [18]
Holding voltage: -110.0 mV
3β-OH Small molecule or natural product Click here for species-specific activity table Rn Pore blocker 5.5 pIC50 - - 1
⤷ pIC50 5.5 (IC50 3x10-6 M) [1]
Description: Inhibition of currents via native Cav3.2 currents in rat dorsal root ganglion cells.
flunarizine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.4 pIC50 - -100.0 37
⤷ pIC50 5.4 [37]
Holding voltage: -100.0 mV
Ni2+ Click here for species-specific activity table Hs Pore blocker 4.9 – 5.2 pIC50 - -90.0 24
⤷ pIC50 4.9 – 5.2 (IC50 1.2x10-5 – 5.7x10-6 M) [24]
Holding voltage: -90.0 mV
View species-specific channel blocker tables
Channel Blocker Comments
Block produced by Ni2+ is voltage dependent [24]. ML218 was developed by NIH’s Molecular Libraries Production Center and is freely available without intellectual property restrictions [54]. For reviews of all known blockers see references [13,16,29,54].
Tissue Distribution Click here for help
Putamen > amygdala, caudate nucleus > frontal lobe, hippocampus, cerebellum, substantia nigra > thalamus > medulla, spinal cord, occipital lobe, temporal lobe.
Species:  Human
Technique:  Northern Blot
References:  45,53
Kidney > liver > heart, brain.> lung, skeletal muscle, pancreas, placenta
Species:  Human
Technique:  Northern Blot
References:  10,53
Hippocampus, striatum > olfactory > cortical subplate > pallidum > isocortex, hypothalamus, midbrain > thalamus > medulla, pons.
Species:  Mouse
Technique:  In situ hybridisation
References:  26
Atrio-ventricular node.
Species:  Rat
Technique:  In situ hybridisation.
References:  27
Soma and proximal dendrites in hippocampus.
Species:  Rat
Technique:  Immunohistochemistry
References:  30
Olfactory bulb, indusium griseum, hippocampus > pineal gland, sensory ganglia > pituitary gland > amygdala.
Species:  Rat
Technique:  In situ hybridisation
References:  46
Adrenal glomerulosa.
Species:  Rat
Technique:  In situ hybridisation
References:  39
Functional Assays Click here for help
Patch clamp electrophysiology.
Species:  Rat
Tissue:  Recombinant Cav3.2 stably expressed in Xenopus laevis oocytes
Response measured:  Electrophysiological measurement of ICa.
References:  35
Patch-clamp (whole cell currents).
Species:  Human
Tissue:  Recombinant Cav3.2 stably expressed in HEK 293 cells.
Response measured:  Electrophysiological measurement of ICa.
References:  14
Fluorometric imaging.
Species:  Human
Tissue:  Recombinant Cav3.2 stably expressed in HEK 293 cells
Response measured:  Fluorescence after loading dye such as Fluo-4.
References:  55
Physiological Functions Click here for help
Nociception (peripheral processing of noxious signals).
Species:  Mouse
Tissue:  Dorsal root ganglion nociceptors.
References:  7
Aldosterone secretion from zona glomerulosa cells.
Species:  Rat
Tissue:  Adrenal gland
References:  39,50
Coronary function (relaxation of coronary arteries).
Species:  Mouse
Tissue:  Heart.
References:  4
Physiological Consequences of Altering Gene Expression Click here for help
Absence of Cav3.2 expression leads to diminished responses to painful stimuli and constitutively constricted coronary arterioles.
Species:  Mouse
Tissue:  Dorsal root ganglion nociceptors, heart
Technique:  Knockout
References:  4,7
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0004112 abnormal arteriole morphology PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0001614 abnormal blood vessel morphology PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0002127 abnormal cardiovascular system morphology PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0003484 abnormal channel response PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0000278 abnormal myocardial fiber morphology PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0003141 cardiac fibrosis PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0001265 decreased body size PMID: 14631046 
Cacna1htm1Kcam Cacna1htm1Kcam/Cacna1htm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J		 MGI:1928842  MP:0003025 increased vasoconstriction PMID: 14631046 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Autism
Synonyms: Autism spectrum disorder [Disease Ontology: DOID:0060041]
Disease Ontology: DOID:0060041
OMIM: 209850
Orphanet: ORPHA106
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R212C 45
Missense Human R902W 45
Missense Human W962C 45
Missense Human A1874V 45
Disease:  Epilepsy, childhood absence, susceptibility to, 6; ECA6
Synonyms: Childhood absence epilepsy [Orphanet: ORPHA64280] [Disease Ontology: DOID:1825]
Disease Ontology: DOID:1825
OMIM: 611942
Orphanet: ORPHA64280
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F161L 5,51
Missense Human E282K 5,51
Missense Human C456S 5,51
Missense Human G499S 5,51
Missense Human P648L 5,51
Missense Human R744Q 5,51
Missense Human A748V 5,51
Missense Human G773D 5,51
Missense Human G784S 5,51
Missense Human V831M 5,51
Missense Human G848S 5,51
Missense Human D1463N 5,51
Disease:  Epilepsy, idiopathic generalized, susceptibility to, 6; ECA6
Synonyms: Idiopathic generalized epilepsy [Disease Ontology: DOID:1827]
Disease Ontology: DOID:1827
OMIM: 611942
Role:  Thalamic oscillation.
Drugs:  Ethosuximide
Side effects:  Rarely: GI distress, drowsiness, leukopenia.
Therapeutic use:  Absence epilepsy.
References:  9,22,52
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human A480T 17,21
Missense Human P618L 17,21
Missense Human G775D 17,21
Nonsense Human V621X 17
Disease:  Familial Hyperaldosteronism Type IV
OMIM: 607904
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
M1549V Human M1549V 38
Missense Human I1430T 32
Disease:  Heart failure
Role:  Elevated aldosterone and Cav3.2 levels associated.
Drugs:  Efonidipine
Side effects:  No serious side effects reported.
Therapeutic use:  Antihypertensive.
References:  23,34,43
Disease:  Neuropathic pain
Role:  Nociceptive hyperexcitability.
Drugs:  Mibefradil, ethosuximide
Side effects:  N/A
Therapeutic use:  Analgesia.
References:  11
Gene Expression and Pathophysiology Click here for help
Increased Cav3.2 expression.
Tissue or cell type:  Thalamic reticular nucleus
Pathophysiology:  Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model
Species:  Rat
Technique:  Various
References:  47,49
Biologically Significant Variant Comments
Multiple splice variants of Cav3.2 exist, particularly with alternative use of exon 25C and 26 which affects the III-IV linker, and which alter the voltage dependence of activation and inactivation as well as the kinetics of the protein [56].
General Comments
The precise role of the Cav3.2 channels in the human cardiovascular system has not been resolved. Although rodents express T-type currents in atrial and pacemaker cells, these have not been detected in man. Some antihypertensive drugs of the dihydropyridine class (e.g. efonidipine) may have a renoprotective effect due to block of T-currents and relaxation of glomerular efferent arterioles [20].

References

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1. Atluri N, Joksimovic SM, Oklopcic A, Milanovic D, Klawitter J, Eggan P, Krishnan K, Covey DF, Todorovic SM, Jevtovic-Todorovic V. (2018) A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain. Br J Anaesth, 120 (4): 768-778. [PMID:29576117]

2. Bezençon O, Heidmann B, Siegrist R, Stamm S, Richard S, Pozzi D, Corminboeuf O, Roch C, Kessler M, Ertel EA et al.. (2017) Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies. J Med Chem, 60 (23): 9769-9789. [PMID:29116786]

3. Chemin J, Monteil A, Perez-Reyes E, Nargeot J, Lory P. (2001) Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide. EMBO J, 20 (24): 7033-40. [PMID:11742980]

4. Chen CC, Lamping KG, Nuno DW, Barresi R, Prouty SJ, Lavoie JL, Cribbs LL, England SK, Sigmund CD, Weiss RM, Williamson RA, Hill JA, Campbell KP. (2003) Abnormal coronary function in mice deficient in alpha1H T-type Ca2+ channels. Science, 302 (5649): 1416-8. [PMID:14631046]

5. Chen Y, Lu J, Pan H, Zhang Y, Wu H, Xu K, Liu X, Jiang Y, Bao X, Yao Z et al.. (2003) Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol, 54 (2): 239-43. [PMID:12891677]

6. Choe W, Messinger RB, Leach E, Eckle VS, Obradovic A, Salajegheh R, Jevtovic-Todorovic V, Todorovic SM. (2011) TTA-P2 is a potent and selective blocker of T-type calcium channels in rat sensory neurons and a novel antinociceptive agent. Mol Pharmacol, 80 (5): 900-10. [PMID:21821734]

7. Choi S, Na HS, Kim J, Lee J, Lee S, Kim D, Park J, Chen CC, Campbell KP, Shin HS. (2007) Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav, 6 (5): 425-31. [PMID:16939637]

8. Chuang RS, Jaffe H, Cribbs L, Perez-Reyes E, Swartz KJ. (1998) Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nat Neurosci, 1 (8): 668-74. [PMID:10196582]

9. Coulter DA, Huguenard JR, Prince DA. (1989) Characterization of ethosuximide reduction of low-threshold calcium current in thalamic neurons. Ann Neurol, 25 (6): 582-93. [PMID:2545161]

10. Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E. (1998) Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res, 83 (1): 103-9. [PMID:9670923]

11. Dogrul A, Gardell LR, Ossipov MH, Tulunay FC, Lai J, Porreca F. (2003) Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain, 105 (1-2): 159-68. [PMID:14499432]

12. Francois A, Kerckhove N, Meleine M, Alloui A, Barrere C, Gelot A, Uebele VN, Renger JJ, Eschalier A, Ardid D et al.. (2013) State-dependent properties of a new T-type calcium channel blocker enhance Ca(V)3.2 selectivity and support analgesic effects. Pain, 154 (2): 283-93. [PMID:23257507]

13. Giordanetto F, Knerr L, Wållberg A. (2011) T-type calcium channels inhibitors: a patent review. Expert Opin Ther Pat, 21 (1): 85-101. [PMID:21087200]

14. Gomora JC, Daud AN, Weiergräber M, Perez-Reyes E. (2001) Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol, 60 (5): 1121-32. [PMID:11641441]

15. Gomora JC, Murbartián J, Arias JM, Lee JH, Perez-Reyes E. (2002) Cloning and expression of the human T-type channel Ca(v)3.3: insights into prepulse facilitation. Biophys J, 83 (1): 229-41. [PMID:12080115]

16. Heady TN, Gomora JC, Macdonald TL, Perez-Reyes E. (2001) Molecular pharmacology of T-type Ca2+ channels. Jpn J Pharmacol, 85 (4): 339-50. [PMID:11388636]

17. Heron SE, Phillips HA, Mulley JC, Mazarib A, Neufeld MY, Berkovic SF, Scheffer IE. (2004) Genetic variation of CACNA1H in idiopathic generalized epilepsy. Ann Neurol, 55 (4): 595-6. [PMID:15048902]

18. Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z. (2014) A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats. Biochem Pharmacol, 89 (4): 536-44. [PMID:24726441]

19. Kasanami Y, Ishikawa C, Kino T, Chonan M, Toyooka N, Takashima Y, Iba Y, Sekiguchi F, Tsubota M, Ohkubo T et al.. (2022) Discovery of pimozide derivatives as novel T-type calcium channel inhibitors with little binding affinity to dopamine D2 receptors for treatment of somatic and visceral pain. Eur J Med Chem, 243: 114716. [PMID:36075145]

20. Kawabata M, Ogawa T, Han WH, Takabatake T. (1999) Renal effects of efonidipine hydrochloride, a new calcium antagonist, in spontaneously hypertensive rats with glomerular injury. Clin Exp Pharmacol Physiol, 26 (9): 674-9. [PMID:10499155]

21. Khosravani H, Bladen C, Parker DB, Snutch TP, McRory JE, Zamponi GW. (2005) Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy. Ann Neurol, 57 (5): 745-9. [PMID:15852375]

22. Klassen T, Davis C, Goldman A, Burgess D, Chen T, Wheeler D, McPherson J, Bourquin T, Lewis L, Villasana D et al.. (2011) Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell, 145 (7): 1036-48. [PMID:21703448]

23. Lalevée N, Rebsamen MC, Barrère-Lemaire S, Perrier E, Nargeot J, Bénitah JP, Rossier MF. (2005) Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes. Cardiovasc Res, 67 (2): 216-24. [PMID:15919070]

24. Lee JH, Gomora JC, Cribbs LL, Perez-Reyes E. (1999) Nickel block of three cloned T-type calcium channels: low concentrations selectively block alpha1H. Biophys J, 77 (6): 3034-42. [PMID:10585925]

25. Lee TS, Kaku T, Takebayashi S, Uchino T, Miyamoto S, Hadama T, Perez-Reyes E, Ono K. (2006) Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms. Pharmacology, 78 (1): 11-20. [PMID:16899990]

26. 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]

27. Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, Lei M, Escande D, Demolombe S. (2005) Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart. J Physiol, 562 (Pt 1): 223-34. [PMID:15498808]

28. Martin RL, Lee JH, Cribbs LL, Perez-Reyes E, Hanck DA. (2000) Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther, 295 (1): 302-8. [PMID:10991994]

29. McGivern JG. (2006) Pharmacology and drug discovery for T-type calcium channels. CNS Neurol Disord Drug Targets, 5 (6): 587-603. [PMID:17168744]

30. McKay BE, McRory JE, Molineux ML, Hamid J, Snutch TP, Zamponi GW, Turner RW. (2006) Ca(V)3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur J Neurosci, 24 (9): 2581-94. [PMID:17100846]

31. McRory JE, Santi CM, Hamming KS, Mezeyova J, Sutton KG, Baillie DL, Stea A, Snutch TP. (2001) Molecular and functional characterization of a family of rat brain T-type calcium channels. J Biol Chem, 276 (6): 3999-4011. [PMID:11073957]

32. Nanba K, Blinder AR, Rege J, Hattangady NG, Else T, Liu CJ, Tomlins SA, Vats P, Kumar-Sinha C, Giordano TJ et al.. (2020) Somatic CACNA1H Mutation As a Cause of Aldosterone-Producing Adenoma. Hypertension, 75 (3): 645-649. [PMID:31983310]

33. Nelson MT, Joksovic PM, Perez-Reyes E, Todorovic SM. (2005) The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors. J Neurosci, 25 (38): 8766-75. [PMID:16177046]

34. Okayama S, Imagawa K, Naya N, Iwama H, Somekawa S, Kawata H, Horii M, Nakajima T, Uemura S, Saito Y. (2006) Blocking T-type Ca2+ channels with efonidipine decreased plasma aldosterone concentration in healthy volunteers. Hypertens Res, 29 (7): 493-7. [PMID:17044661]

35. Park JH, Choi JK, Lee E, Lee JK, Rhim H, Seo SH, Kim Y, Doddareddy MR, Pae AN, Kang J, Roh EJ. (2007) Lead discovery and optimization of T-type calcium channel blockers. Bioorg Med Chem, 15 (3): 1409-19. [PMID:17150365]

36. Remen L, Bezençon O, Simons L, Gaston R, Downing D, Gatfield J, Roch C, Kessler M, Mosbacher J, Pfeifer T et al.. (2016) Preparation, Antiepileptic Activity, and Cardiovascular Safety of Dihydropyrazoles as Brain-Penetrant T-Type Calcium Channel Blockers. J Med Chem, 59 (18): 8398-411. [PMID:27579577]

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