Voltage-gated calcium channels (Ca<sub>V</sub>) | Ion channels | IUPHAR/BPS Guide to MALARIA PHARMACOLOGY

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Voltage-gated ion channels
Voltage-gated calcium channels (Ca_V)

Voltage-gated calcium channels (Ca_V) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Ca²⁺ channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca²⁺channels was proposed by [14] and approved by the NC-IUPHAR Subcommittee on Ca²⁺ channels [9]. Most Ca²⁺ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, Ca_V1.x) channels; (2) the high- to moderate-voltage activated dihydropyridine-insensitive (Ca_V2.x) channels and (3) the low-voltage-activated (T-type, Ca_V3.x) channels. Each α1 subunit has four homologous repeats (I-IV), each repeat having six transmembrane domains (S1-S6) forming a voltage-sensing domain (VSD, S1-S4) coupled to a pore-forming module (S5, S6 and their connecting linker that contains the selectivity filter. Voltage-dependent gating is driven by voltage-induced transmembrane movements of the S4-helix enabled by conserved positive charges interacting with negative counter-charges within the VSD [8]. All of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2-δ subunits. CACHD1 is an α2δ-like protein that modulates Ca_v3 channel activity [12]. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Ca_v1.1 channel. The α2-δ1 and α2-δ2 subunits bind gabapentin and pregabalin [10].

Channels and Subunits

Ca_v1.1 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

528

Nomenclature

Ca_v1.1

Previous and unofficial names

Genes

CACNA1S (Hs), Cacna1s (Mm), Cacna1s (Rn)

Ensembl ID

ENSG00000081248 (Hs), ENSMUSG00000026407 (Mm), ENSRNOG00000046231 (Rn)

UniProtKB AC

Q13698 (Hs), Q02789 (Mm), Q02485 (Rn)

Activators

FPL64176 pEC₅₀ ~7.8

(-)-(S)-BayK8644 pEC₅₀ ~7.8

Gating inhibitors

nifedipine pIC₅₀ 6.3 [voltage dependent -90.0 mV] [23] - Rat

nimodipine pIC₅₀ ~6.0 [-70.0 mV]

Channel blockers

verapamil pIC₅₀ ~5.0 [100.0 mV] [46] - Rabbit

diltiazem pIC₅₀ 4.2 [-100.0 mV] [46] - Rabbit

Functional characteristics

L-type calcium current: High voltage-activated, very slow voltage dependent inactivation

Comment

Serves primarily as voltage-sensor for excitation contraction coupling in skeletal muscle. The adaptor protein STAC3 binds to Ca_v1.1 α1 and is essential for transmitting its conformational changes to ryanodine receptor-mediated excitation contraction coupling [37].

Ca_v1.2 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

529

Nomenclature

Ca_v1.2

Previous and unofficial names

Genes

CACNA1C (Hs), Cacna1c (Mm), Cacna1c (Rn)

Ensembl ID

ENSG00000151067 (Hs), ENSMUSG00000051331 (Mm), ENSRNOG00000007090 (Rn)

UniProtKB AC

Q13936 (Hs), Q01815 (Mm), P22002 (Rn)

Activators

FPL64176 Concentration range: 1x10^-7 - 1x10^-6 M [21,28]

(-)-(S)-BayK8644 pEC₅₀ ~7.8

Gating inhibitors

amlodipine pIC₅₀ 9.3 [17] - Rabbit

isradipine pIC₅₀ 8.8 (arterial smooth muscle-like activity) [35], 8.5 (dopamine neuron neuron-like activity) [35]

nifedipine pIC₅₀ 8.1 – 8.7 [-40.0 mV] (100-fold difference for nifedipine on rat smooth (pIC50 8.5) versus cardiac (pIC50 6.5) cells in vitro (Perez-Vizcaino et al. 1993).) [36,38] - Rat

nimodipine pIC₅₀ 6.8 [-80.0 mV] [50] - Rat

Channel blockers

diltiazem pIC₅₀ 6.3 [20] - Ferret

verapamil pIC₅₀ 5.3 – 6.5 [19] - Rat

Sub/family-selective channel blockers

calciseptine pIC₅₀ 7.1 – 7.8 [3,13,32,47]

Functional characteristics

L-type calcium current: High voltage-activated, voltage- and calcium-dependent inactivation

Comment

Amlodopine, isradipine, nifedipine and nimodipine are examples of dihydropyridine calcium channel antagonists. Verapamil is a phenylalkylamine calcium channel blocker. Diltiazem is an example of a benzothiazepine calcium channel blocker. Inhibition by dihydropyridines (e.g. nifedipine or isradipine) is voltage-dependent with a higher apparent affinity at more depolarised potentials [42]; phenylalkylamines and diltiazem exhibit strong use-dependence with a higher apparent affinity at higher stimulation frequencies. Calciseptin is a potent inhibitor of Ca_v1.2 but not of Ca_v1.3 [32].

Ca_v1.3 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

530

Nomenclature

Ca_v1.3

Previous and unofficial names

Genes

CACNA1D (Hs), Cacna1d (Mm), Cacna1d (Rn)

Ensembl ID

ENSG00000157388 (Hs), ENSMUSG00000015968 (Mm), ENSRNOG00000013147 (Rn)

UniProtKB AC

Q01668 (Hs), Q99246 (Mm), P27732 (Rn)

Activators

FPL64176 pEC₅₀ ~7.8

(-)-(S)-BayK8644 pEC₅₀ ~7.8

Gating inhibitors

nitrendipine pIC₅₀ 8.4 [41]

isradipine pIC₅₀ 7.8 – 8.2 (dopamine neuron-like activity; splice variant-dependent) [35]

nifedipine pIC₅₀ 7.7 [41]

nimodipine pIC₅₀ 5.7 – 6.6 [-80.0 – -40.0 mV] [39,50] - Rat

Channel blockers

verapamil pIC₅₀ 3.7 [-70.0 mV] [44] - Mouse

diltiazem pIC₅₀ 3.5 [-70.0 mV] [44] - Mouse

Functional characteristics

L-type calcium current: more negative activation voltage range than Ca_v1.2, calcium-dependent inactivation

Comment

Ca_v1.3 is about 5-10 fold less sensitive to dihydropyridine antagonists [42].

Ca_v1.4 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

531

Nomenclature

Ca_v1.4

Previous and unofficial names

Genes

CACNA1F (Hs), Cacna1f (Mm), Cacna1f (Rn)

Ensembl ID

ENSG00000102001 (Hs), ENSMUSG00000031142 (Mm), ENSRNOG00000010348 (Rn)

UniProtKB AC

O60840 (Hs), Q9JIS7 (Mm)

Activators

(-)-(S)-BayK8644 pEC₅₀ ~7.8

Gating inhibitors

nitrendipine pIC₅₀ ~6.0 [-70.0 mV]

nifedipine pIC₅₀ 6.0 [-100.0 mV] [31]

nimodipine pIC₅₀ ~6.0 [-70.0 mV]

Channel blockers

verapamil Concentration range: 1x10^-4 M [-80.0 mV] [4] - Mouse

diltiazem pIC₅₀ 4.0 [-80.0 mV] [4] - Mouse

Functional characteristics

L-type calcium current: More negative activation voltage range than Ca_v1.2, no/weak calcium-dependent inactivation

Comment

Ca_v1.4 is less sensitive to dihydropyridine antagonists than other Ca_v1 channels

Ca_v2.1 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

532

Nomenclature

Ca_v2.1

Previous and unofficial names

Genes

CACNA1A (Hs), Cacna1a (Mm), Cacna1a (Rn)

Ensembl ID

ENSG00000141837 (Hs), ENSMUSG00000034656 (Mm), ENSRNOG00000052707 (Rn)

UniProtKB AC

O00555 (Hs), P97445 (Mm), P54282 (Rn)

Selective gating inhibitors

ω-agatoxin IVB pK_d 8.5 [-80.0 mV] [1] - Rat

ω-agatoxin IVA pIC₅₀ 7.0 – 8.7 [-100.0 – -90.0 mV] (P current component: Kd =~2nM, Q component Kd= >100nM) [7,33] - Rat

Sub/family-selective channel blockers

ω-conotoxin MVIIC pIC₅₀ 8.2 – 9.2 Concentration range: 2x10^-6 - 5x10^-6 M [Physiological voltage] [26] - Rat

Functional characteristics

P/Q-type calcium current: High voltage-activated, moderate voltage-dependent inactivation

Comment

All three Ca_v2.x types directly contribute towards triggering neurotransmitter release at fast synapses in the mammalian nervous system. In many cell types, P- and Q-current components cannot be adequately separated and many researchers in the field have therefore adopted the terminology 'P/Q-type' current when referring to either component. Both of these physiologically defined current types are conducted by alternative forms of Ca_v2.1 [27]. Ziconotide (a synthetic peptide equivalent to omega-Conotoxin-MVIIA) has been approved for the treatment of chronic pain [48].

Ca_v2.2 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

533

Nomenclature

Ca_v2.2

Previous and unofficial names

Genes

CACNA1B (Hs), Cacna1b (Mm), Cacna1b (Rn)

Ensembl ID

ENSG00000148408 (Hs), ENSMUSG00000004113 (Mm), ENSRNOG00000004560 (Rn)

UniProtKB AC

Q00975 (Hs), O55017 (Mm), Q02294 (Rn)

Gating inhibitors

NP118809 pIC₅₀ 7.0 [-80.0 mV] [51] - Rat

Selective gating inhibitors

C2230 pIC₅₀ 6.0 [-50.0 mV] [43]

Sub/family-selective channel blockers

ω-conotoxin GVIA pIC₅₀ 10.4 [-80.0 mV] [26] - Rat

ω-conotoxin MVIIC pIC₅₀ 6.1 – 8.5 [-80.0 mV] [16,26,30] - Rat

Functional characteristics

N-type calcium current: High voltage-activated, moderate voltage-dependent inactivation

Ca_v2.3 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

534

Nomenclature

Ca_v2.3

Previous and unofficial names

Genes

CACNA1E (Hs), Cacna1e (Mm), Cacna1e (Rn)

Ensembl ID

ENSG00000198216 (Hs), ENSMUSG00000004110 (Mm), ENSRNOG00000002863 (Rn)

UniProtKB AC

Q15878 (Hs), Q61290 (Mm), Q07652 (Rn)

Selective gating inhibitors

SNX482 pIC₅₀ 7.5 – 8.0 [Physiological voltage] [34]

Channel blockers

Ni²⁺ pIC₅₀ 4.6 [-90.0 mV] [49]

Functional characteristics

R-type calcium current: Moderate voltage-activated, fast voltage-dependent inactivation

Ca_v3.1 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

535

Nomenclature

Ca_v3.1

Previous and unofficial names

NBR13 | alpha-1G | calcium channel

Genes

CACNA1G (Hs), Cacna1g (Mm), Cacna1g (Rn)

Ensembl ID

ENSG00000006283 (Hs), ENSMUSG00000020866 (Mm), ENSRNOG00000060528 (Rn)

UniProtKB AC

O43497 (Hs), O54898 (Rn)

Gating inhibitors

kurtoxin pIC₅₀ 7.3 – 7.8 [-90.0 mV] [11,40] - Rat

Channel blockers

ACT-709478 pIC₅₀ 8.2 [6]

ulixacaltamide pIC₅₀ 7.3 [-80.0 mV] (voltage-dependent) [45]

TTA-A2 pIC₅₀ 7.0 [-75.0 mV] (voltage-dependent) [15]

mibefradil pIC₅₀ 6.0 – 6.6 [-110.0 – -100.0 mV] [29]

Ni²⁺ pIC₅₀ 3.6 – 3.8 [voltage dependent -90.0 mV] [24] - Rat

Functional characteristics

T-type calcium current: Low voltage-activated, fast voltage-dependent inactivation

Ca_v3.2 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

536

Nomenclature

Ca_v3.2

Previous and unofficial names

a1H | alpha-1H | calcium channel

Genes

CACNA1H (Hs), Cacna1h (Mm), Cacna1h (Rn)

Ensembl ID

ENSG00000196557 (Hs), ENSMUSG00000024112 (Mm), ENSRNOG00000033893 (Rn)

UniProtKB AC

O95180 (Hs), O88427 (Mm), Q9EQ60 (Rn)

Gating inhibitors

kurtoxin pIC₅₀ 7.3 – 7.6 [-90.0 mV] [11,40] - Rat

Channel blockers

TTA-A2 pIC₅₀ 8.0 [-75.0 mV] [15]

ACT-709478 pIC₅₀ 7.7 [6]

and derivatives pimozide pIC₅₀ 6.8 [22]

ulixacaltamide pIC₅₀ 6.8 [-75.0 mV] (voltage-dependent) [45]

mibefradil pIC₅₀ 5.9 – 7.2 [-110.0 – -80.0 mV] [29]

efonidipine pIC₅₀ 6.4 [25]

ABT-639 pIC₅₀ 5.7 [-70.0 mV] [2,18]

Ni²⁺ pIC₅₀ 4.9 – 5.2 [voltage dependent -90.0 mV] [24]

Functional characteristics

T-type calcium current: Low voltage-activated, fast voltage-dependent inactivation

Ca_v3.3 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

537

Nomenclature

Ca_v3.3

Previous and unofficial names

α1I | Ca_vT.3 | low voltage-activated T-type calcium channel alpha-1 subunit (CACNA1I) | alpha-1I | calcium channel

Genes

CACNA1I (Hs), Cacna1i (Mm), Cacna1i (Rn)

Ensembl ID

ENSG00000100346 (Hs), ENSMUSG00000022416 (Mm), ENSRNOG00000060407 (Rn)

UniProtKB AC

Q9P0X4 (Hs), Q9Z0Y8 (Rn)

Channel blockers

ACT-709478 pIC₅₀ 8.1 [6]

TTA-A2 pIC₅₀ 7.5 [-75.0 mV] (voltage-dependent) [15]

ulixacaltamide pIC₅₀ 7.0 [-75.0 mV] (voltage-dependent) [45]

mibefradil pIC₅₀ 5.8 [-110.0 mV] [29]

Ni²⁺ pIC₅₀ 3.7 – 4.1 [voltage dependent -90.0 mV] [24] - Rat

Functional characteristics

T-type calcium current: Low voltage-activated, moderate voltage-dependent inactivation

References

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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. Antunes FTT, Huang S, Chen L, Zamponi GW. (2024) Effect of ABT-639 on Cav3.2 channel activity and its analgesic actions in mouse models of inflammatory and neuropathic pain. Eur J Pharmacol, 967: 176416. [PMID:38342359]

3. Barrere C, Chinda K, Mesirca P, Aurelie C, Diochot S, Lazdunsk M, Barrere-Lamaire S, Mangoni M, Nargeot J. (2020) Evidence for a selective blockade of Cav1.2 versus Cav1.3 by the mamba toxin calciseptine in the mouse heart. Archives of Cardiovascular Diseases Supplements, 12 (2-4): 259. DOI: 10.1016/j.acvdsp.2020.03.144

4. Baumann L, Gerstner A, Zong X, Biel M, Wahl-Schott C. (2004) Functional characterization of the L-type Ca2+ channel Cav1.4alpha1 from mouse retina. Invest Ophthalmol Vis Sci, 45 (2): 708-13. [PMID:14744918]

5. Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce WG, Koop B, Fishman GA, Mets M, Musarella MA, Boycott KM. (1998) Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nat Genet, 19 (3): 264-7. [PMID:9662400]

6. 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]

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. Catterall WA, Lenaeus MJ, Gamal El-Din TM. (2020) Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels. Annu Rev Pharmacol Toxicol, 60: 133-154. [PMID:31537174]

9. Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev, 57 (4): 411-25. [PMID:16382099]

10. Chen Z, Mondal A, Minor Jr DL. (2023) Structural basis for Ca_Vα₂δ:gabapentin binding. Nat Struct Mol Biol, 30 (6): 735-739. [PMID:36973510]

11. 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]

12. Cottrell GS, Soubrane CH, Hounshell JA, Lin H, Owenson V, Rigby M, Cox PJ, Barker BS, Ottolini M, Ince S et al.. (2018) CACHD1 is an α2δ-Like Protein That Modulates Ca_V3 Voltage-Gated Calcium Channel Activity. J Neurosci, 38 (43): 9186-9201. [PMID:30181139]

13. de Weille JR, Schweitz H, Maes P, Tartar A, Lazdunski M. (1991) Calciseptine, a peptide isolated from black mamba venom, is a specific blocker of the L-type calcium channel. Proc Natl Acad Sci U S A, 88 (6): 2437-40. [PMID:1848702]

14. Ertel EA, Campbell KP, Harpold MM, Hofmann F, Mori Y, Perez-Reyes E, Schwartz A, Snutch TP, Tanabe T, Birnbaumer L, Tsien RW, Catterall WA. (2000) Nomenclature of voltage-gated calcium channels. Neuron, 25 (3): 533-5. [PMID:10774722]

15. 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]

16. 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]

17. Hughes AD, Wijetunge S. (1993) The action of amlodipine on voltage-operated calcium channels in vascular smooth muscle. Br J Pharmacol, 109 (1): 120-5. [PMID:8388295]

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. Johnson BD, Hockerman GH, Scheuer T, Catterall WA. (1996) Distinct effects of mutations in transmembrane segment IVS6 on block of L-type calcium channels by structurally similar phenylalkylamines. Mol Pharmacol, 50 (5): 1388-400. [PMID:8913371]

20. Kanaya S, Katzung BG. (1984) Effects of diltiazem on transmembrane potential and current of right ventricular papillary muscle of ferrets. J Pharmacol Exp Ther, 228 (1): 245-51. [PMID:6694106]

21. Kang J, Chen XL, Ji J, Lei Q, Rampe D. (2012) Ca²⁺ channel activators reveal differential L-type Ca²⁺ channel pharmacology between native and stem cell-derived cardiomyocytes. J Pharmacol Exp Ther, 341 (2): 510-7. [PMID:22353878]

22. 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]

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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. 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]

27. Li Z, Cong Y, Wu T, Wang T, Lou X, Yang X, Yan N. (2024) Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Ca_v2.1 channels. Cell Res, 34 (6): 455-457. [PMID:38443561]

28. Liu L, Gonzalez PK, Barrett CF, Rittenhouse AR. (2003) The calcium channel ligand FPL 64176 enhances L-type but inhibits N-type neuronal calcium currents. Neuropharmacology, 45 (2): 281-92. [PMID:12842134]

29. 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]

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31. McRory JE, Hamid J, Doering CJ, Garcia E, Parker R, Hamming K, Chen L, Hildebrand M, Beedle AM, Feldcamp L et al.. (2004) The CACNA1F gene encodes an L-type calcium channel with unique biophysical properties and tissue distribution. J Neurosci, 24 (7): 1707-18. [PMID:14973233]

32. Mesirca P, Chemin J, Barrère C, Torre E, Gallot L, Monteil A, Bidaud I, Diochot S, Lazdunski M, Soong TW et al.. (2024) Selective blockade of Ca_v1.2 (α1C) versus Ca_v1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine. Nat Commun, 15 (1): 54. [PMID:38167790]

33. 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]

34. Newcomb R, Szoke B, Palma A, Wang G, Chen Xh, Hopkins W, Cong R, Miller J, Urge L, Tarczy-Hornoch K et al.. (1998) Selective peptide antagonist of the class E calcium channel from the venom of the tarantula Hysterocrates gigas. Biochemistry, 37 (44): 15353-62. [PMID:9799496]

35. Ortner NJ, Bock G, Dougalis A, Kharitonova M, Duda J, Hess S, Tuluc P, Pomberger T, Stefanova N, Pitterl F et al.. (2017) Lower Affinity of Isradipine for L-Type Ca²⁺ Channels during Substantia Nigra Dopamine Neuron-Like Activity: Implications for Neuroprotection in Parkinson's Disease. J Neurosci, 37 (28): 6761-6777. [PMID:28592699]

36. Pignier C, Potreau D. (2000) Characterization of nifedipine-resistant calcium current in neonatal rat ventricular cardiomyocytes. Am J Physiol Heart Circ Physiol, 279 (5): H2259-68. [PMID:11045961]

37. Polster A, Perni S, Bichraoui H, Beam KG. (2015) Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca2+ channels. Proc Natl Acad Sci U S A, 112 (2): 602-6. [PMID:25548159]

38. Pérez-Vizcaíno F, Tamargo J, Hof RP, Rüegg UT. (1993) Vascular selectivity of seven prototype calcium antagonists: a study at the single cell level. J Cardiovasc Pharmacol, 22 (5): 768-75. [PMID:7506331]

39. Safa P, Boulter J, Hales TG. (2001) Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants expressed by rat brain and neuroendocrine GH3 cells. J Biol Chem, 276 (42): 38727-37. [PMID:11514547]

40. 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]

41. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J. (2009) Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol, 75 (2): 407-14. [PMID:19029287]

42. Török F, Salamon S, Ortner NJ, Fernández-Quintero ML, Matthes J, Striessnig J. (2025) Inactivation induced by pathogenic Ca_v1.3 L-type Ca²⁺-channel variants enhances sensitivity for dihydropyridine Ca²⁺ channel blockers. Br J Pharmacol, 182 (1): 181-197. [PMID:39370994]

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NC-IUPHAR subcommittee and family contributors

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Subcommittee members:

Jörg Striessnig (Chairperson)
Pharmacology and Toxicology, Institute of Pharmacy
Center for Molecular Biosciences
University of Innsbruck
Center for Chemistry and Biomedicine
Innrain 80-82/III
A-6020 Innsbruck, Austria

William A. Catterall
(1946-2024)
Formerly of the Department of Pharmacology
University of Washington
Seattle
USA

Edward Perez-Reyes
Department of Pharmacology
Box 800735
University of Virginia
1300 Jefferson Park Ave
Charlottesville
VA 22911
USA

Terrance P. Snutch
Michael Smith Laboratories
The University of British Columbia
#301 - 2185 East Mall
Vancouver, BC
V6T 1Z4
Canada

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Striessnig J, Gibb AJ, Mathie AA, Veale EL, Kelly E, Peach CJ, Armstrong JF, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Ion channels. Br J Pharmacol. 182: S152-S241.