CaV1.4 channels

Channel name Cav1.4
Description Voltage-gated calcium channel α1 subunit
Other names α1F
Molecular information Human: 1966aa, AJ224874 (PMID: 9662399); chr. Xp11.23, CACNA1F, LocusID: 778
Rat: 1981aa, AF365975 (PMID: 11526344); chr. Xq22, Cacna1f, LocusID: 114493
Mouse: 1985aa, AF192497 (PMID: 10873387); chr. X, Cacna1f, LocusID: 54652
Associated subunits Not established; preliminary functional evidence for β2 association in retinal neurons1
Functional assays Patch-clamp (whole-cell, single-channel), calcium imaging
Current ICa,L
Conductance Preliminary evidence for very small single channel conductance (less than half of Cav1.2); Ba2+ > Ca2+2,4,6
Ion selectivity Not established
Activation Va = -2.5 to -12 mV (2–20 mM Ca2+ or 15–20 mM Ba2+; HEK cells)3,4,5,6; τa < 1 ms at Vmax (but slower components were also observed)3,6
Inactivation Vh = -9 to -27 mV (10–20 mM Ba2+, HEK cells)4,6; inactivation kinetics even slower than those of Cav1.3 with incomplete inactivation during 10-s depolarizations to Vmax3; calcium-induced inactivation is not observed for Cav1.4 channels expressed in HEK cells3,4,6 but after expression in Xenopus oocytes2
Activators BayK86442,3,4,6
Gating modifiers Dihydropyridine antagonists: nifedipine (IC50 = 944 nM at - 100 mV, ∼300 nM at -50 mV4; isradipine: ∼80% inhibition by 100 nM at -50 mV3,6 and 1 μM at -90 mV)3; d-cis-diltiazem (IC50=92 μM); verapamil: 69% inhibition at 100 μM (0.2 Hz, holding potential = -80 mV)6
Blockers Nonselective: Cd2+2
Radioligands Unlike for Cav1.2 and Cav1.3, no high-affinity (+)-[3H]isradipine binding detectable (HEK cells) (J. Striessnig, unpublished observations)
Channel distribution Retinal photoreceptors and bipolar cells, spinal cord, lymphoid tissue (plasma and mast cells)1,4,7,8,9,10
Physiological functions Neurotransmitter release in retinal cells
Mutations and pathophysiology Mutations cause X-linked congenital stationary night blindness type 27,9,11,12
Pharmacological significance Not established
Comments The biophysical properties of heterologously expressed Cav1.4 channels resemble those recorded in retinal neurons, suggesting that this channel type underlies retinal ICa,L–however, similar to Cav1.4, Cav1.3 channels also inactivate slowly and activate rapidly and may therefore also contribute to retinal ICa,L
  • aa, amino acids; chr., chromosome; HEK, human embryonic kidney.

  • 1. Ball SL, Powers PA, Shin HS, Morgans CW, Peachey NS, and Gregg RG (2002) Role of the β2 subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Investig Ophthalmol Vis Sci 43:1595-1603

  • 2. Hoda JC, Zaghetto F, Koschak A, and Striessnig J (2005) CSNB2 mutations S229P, G369D, L1068P, and W1440X alter channel gating or functional expression of Cav1.4 L-type Ca2+ channels. J Biol Chem 25:252-259

  • 3. Koschak A, Reimer D, Walter D, Hoda JC, Heinzle T, Grabner M, and Striessnig J (2003) Cav1.4 α1 subunits can form slowly in activating dihydropyridine-sensitive L-type Ca2+ channels lacking Ca2+-dependent inactivation. J Biol Chem 23:6041-6049

  • 4. 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 Biol Chem 24:1707-1718

  • 5. Haeseleer F, Imanishi Y, Maeda T, Possin DE, Maeda A, Lee A, Rieke F, and Palczewski K (2004) Essential role of Ca2+-bindingprotein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function. Nat Neurosci 7:1079-1087

  • 6. Baumann L, Gerstner A, Zong X, Biel M, and Wahl-Schott C (2004) Functional characterization of the L-type Ca2+ channel Cav1.4 α1 from mouse retina. Investig Ophthalmol Vis Sci 45:708-713

  • 7. Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce WG, Koop B, Fishman GA, Mets M, Musarella MA, and Boycott KM (1998) Loss-of-function mutations in a calcium-channel α1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nat Genet 19:264-267

  • 8. Naylor MJ, Rancourt DE, and Bech-Hansen NT (2000) Isolation and characterization of a calcium channel gene, Cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness. Genomics 66:324-327

  • 9. Strom TM, Nyakatura G, Apfelstedt-Sylla E, Hellebrand H, Lorenz B, Weber BH, Wutz K, Gutwillinger N, Ruther K, Drescher B, et al. (1998) An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nat Genet 19:260-263

  • 10. Firth SI, Morgan IG, Boelen MK, and Morgans CW (2001) Localization of voltage-sensitive L-type calcium channels in the chicken retina. Clin Experiment Ophthalmol 29:183-187

  • 11. CACNA1F; OMIM no. 300110

  • 12. Striessnig J, Hoda JC, Koschak A, Zaghetto F, Mullner C, Sinnegger-Brauns MJ, Wild C, Watschinger K, Trockenbacher A, and Pelster G (2004) L-type Ca2+ channels in Ca2+ channelopathies. Biochem Biophys Res Commun 322:1341-1346