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Science 23 September 1988:
Vol. 241. no. 4873, pp. 1661 - 1664
DOI: 10.1126/science.2458626
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Articles

Science, Vol 241, Issue 4873, 1661-1664
Copyright © 1988 by American Association for the Advancement of Science

articles

Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel

SB Ellis, ME Williams, NR Ways, R Brenner, AH Sharp, AT Leung, KP Campbell, E McKenna, WJ Koch, A Hui, and al. et

Salk Institute Biotechnology/Industrial Associates, Inc., La Jolla, CA 92037.

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.


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Modulation of CaV2.1 Channels by the Neuronal Calcium-Binding Protein Visinin-Like Protein-2.
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J. Neurosci. 25, 7062-7070
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A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation.
A. Hemara-Wahanui, S. Berjukow, C. I. Hope, P. K. Dearden, S.-B. Wu, J. Wilson-Wheeler, D. M. Sharp, P. Lundon-Treweek, G. M. Clover, J.-C. Hoda, et al. (2005)
PNAS 102, 7553-7558
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Sites of proteolytic processing and noncovalent association of the distal C-terminal domain of CaV1.1 channels in skeletal muscle.
J. T. Hulme, K. Konoki, T. W.-C. Lin, M. A. Gritsenko, D. G. Camp II, D. J. Bigelow, and W. A. Catterall (2005)
PNAS 102, 5274-5279
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The Ca2+ Channel {alpha}2{delta}-1 Subunit Determines Ca2+ Current Kinetics in Skeletal Muscle but Not Targeting of {alpha}1S or Excitation-Contraction Coupling.
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Molecular Determinants of Frequency Dependence and Ca2+ Potentiation of Verapamil Block in the Pore Region of Cav1.2.
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Cav1.4{alpha}1 Subunits Can Form Slowly Inactivating Dihydropyridine-Sensitive L-Type Ca2+ Channels Lacking Ca2+-Dependent Inactivation.
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J. Neurosci. 23, 6041-6049
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Cardiac L-type Calcium Channel {beta}-Subunits Expressed in Human Heart Have Differential Effects on Single Channel Characteristics.
R. Hullin, I. F. Y. Khan, S. Wirtz, P. Mohacsi, G. Varadi, A. Schwartz, and S. Herzig (2003)
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Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces ICa,L and Ito in rapid atrial pacing in rabbits.
R. F. Bosch, C. R. Scherer, N. Rub, S. Wohrl, K. Steinmeyer, H. Haase, A. E. Busch, L. Seipel, and V. Kuhlkamp (2003)
J. Am. Coll. Cardiol. 41, 858-869
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Molecular Cloning and Characterization of the Human Voltage-Gated Calcium Channel alpha 2delta -4 Subunit.
N. Qin, S. Yagel, M.-L. Momplaisir, E. E. Codd, and M. R. D'Andrea (2002)
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Structure of the voltage-gated L-type Ca2+ channel by electron cryomicroscopy.
I. I. Serysheva, S. J. Ludtke, M. R. Baker, W. Chiu, and S. L. Hamilton (2002)
PNAS 99, 10370-10375
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The Role of Region IVS5 of the Human Cardiac Calcium Channel in Establishing Inactivated Channel Conformation. USE-DEPENDENT BLOCK BY BENZOTHIAZEPINES.
I. Bodi, S. E. Koch, H. Yamaguchi, G. P. Szigeti, A. Schwartz, and G. Varadi (2002)
J. Biol. Chem. 277, 20651-20659
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The Virally Encoded Fungal Toxin KP4 Specifically Blocks L-Type Voltage-Gated Calcium Channels.
M. J. Gage, S. G. Rane, G. H. Hockerman, and T. J. Smith (2002)
Mol. Pharmacol. 61, 936-944
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Parathyroid cells express dihydropyridine-sensitive cation currents and L-type calcium channel subunits.
W. Chang, S. A. Pratt, T.-H. Chen, C.-L. Tu, G. Mikala, A. Schwartz, and D. Shoback (2001)
Am J Physiol Endocrinol Metab 281, E180-E189
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Calcium Channel alpha 2delta Subunits---Structure and Gabapentin Binding.
E. Marais, N. Klugbauer, and F. Hofmann (2001)
Mol. Pharmacol. 59, 1243-1248
   Abstract »    Full Text »
Molecular Determinants of Diltiazem Block in Domains IIIS6 and IVS6 of L-type Ca2+ Channels.
G. H. Hockerman, N. Dilmac, T. Scheuer, and W. A. Catterall (2001)
Mol. Pharmacol. 58, 1264-1270
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Differential Effect of Gabapentin on Neuronal and Muscle Calcium Currents.
K. J. Alden and J. García (2001)
J. Pharmacol. Exp. Ther. 297, 727-735
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Allosteric modulation of Ca2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Cavbeta subunits.
S. Herlitze, H. Zhong, T. Scheuer, and W. A. Catterall (2001)
PNAS 98, 4699-4704
   Abstract »    Full Text »    PDF »
Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca2+ channel.
H. Zhong, B. Li, T. Scheuer, and W. A. Catterall (2001)
PNAS 98, 4705-4709
   Abstract »    Full Text »    PDF »
Upregulation of Dorsal Root Ganglion {alpha}2{delta} Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats.
Z. D. Luo, S. R. Chaplan, E. S. Higuera, L. S. Sorkin, K. A. Stauderman, M. E. Williams, and T. L. Yaksh (2001)
J. Neurosci. 21, 1868-1875
   Abstract »    Full Text »    PDF »
G protein modulation of recombinant P/Q-type calcium channels by regulators of G protein signalling proteins.
M. D Mark, S. Wittemann, and S. Herlitze (2000)
J. Physiol. 528, 65-77
   Abstract »    Full Text »    PDF »
Functional Properties of a New Voltage-dependent Calcium Channel alpha 2delta Auxiliary Subunit Gene (CACNA2D2).
B. Gao, Y. Sekido, A. Maximov, M. Saad, E. Forgacs, F. Latif, M. H. Wei, M. Lerman, J.-H. Lee, E. Perez-Reyes, et al. (2000)
J. Biol. Chem. 275, 12237-12242
   Abstract »    Full Text »    PDF »
Three New Familial Hemiplegic Migraine Mutants Affect P/Q-type Ca2+ Channel Kinetics.
R. L. Kraus, M. J. Sinnegger, A. Koschak, H. Glossmann, S. Stenirri, P. Carrera, and J. Striessnig (2000)
J. Biol. Chem. 275, 9239-9243
   Abstract »    Full Text »    PDF »
Regulation of Cloned Cardiac L-type Calcium Channels by cGMP-dependent Protein Kinase.
L. H. Jiang, D. J. Gawler, N. Hodson, C. J. Milligan, H. A. Pearson, V. Porter, and D. Wray (2000)
J. Biol. Chem. 275, 6135-6143
   Abstract »    Full Text »    PDF »
The molecular biology of invertebrate voltage-gated Ca(2+) channels.
M. Jeziorski, R. Greenberg, and P. Anderson (2000)
J. Exp. Biol. 203, 841-856
   Abstract »    PDF »
Voltage-dependent facilitation of cardiac L-type Ca channels expressed in HEK-293 cells requires beta -subunit.
T. J. Kamp, H. Hu, and E. Marban (2000)
Am J Physiol Heart Circ Physiol 278, H126-H136
   Abstract »    Full Text »    PDF »
Voltage-Gated Ion Channels and Hereditary Disease.
F. Lehmann-Horn and K. Jurkat-Rott (1999)
Physiol Rev 79, 1317-1372
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Interaction between permeant ions and voltage sensor during inactivation of N-type Ca2+ channels.
R. Shirokov (1999)
J. Physiol. 518, 697-703
   Abstract »    Full Text »    PDF »
Ca channels in cardiac myocytes: structure and function in Ca influx and intracellular Ca release.
D. M Bers and E. Perez-Reyes (1999)
Cardiovasc Res 42, 339-360
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A Region in IVS5 of the Human Cardiac L-type Calcium Channel Is Required for the Use-dependent Block by Phenylalkylamines and Benzothiazepines.
H. K. Motoike, I. Bodi, H. Nakayama, A. Schwartz, and G. Varadi (1999)
J. Biol. Chem. 274, 9409-9420
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Critical role of conserved proline residues in the transmembrane segment 4 voltage sensor function and in the gating of L-type calcium channels.
H. Yamaguchi, J. N. Muth, M. Varadi, A. Schwartz, and G. Varadi (1999)
PNAS 96, 1357-1362
   Abstract »    Full Text »    PDF »
Molecular Diversity of the Calcium Channel alpha 2delta Subunit.
N. Klugbauer, L. Lacinova, E. Marais, M. Hobom, and F. Hofmann (1999)
J. Neurosci. 19, 684-691
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Diltiazem Interaction with L-type Ca2+ Channels.
R. L. Kraus, S. Hering, M. Grabner, D. Ostler, and J. Striessnig (1998)
J. Biol. Chem. 273, 27205-27212
   Abstract »    Full Text »    PDF »
Cloning and Deletion Mutagenesis of the alpha 2delta Calcium Channel Subunit from Porcine Cerebral Cortex. EXPRESSION OF A SOLUBLE FORM OF THE PROTEIN THAT RETAINS [3H]GABAPENTIN BINDING ACTIVITY.
J. P. Brown and N. S. Gee (1998)
J. Biol. Chem. 273, 25458-25465
   Abstract »    Full Text »    PDF »
Molecular Cloning and Functional Expression of a Skeletal Muscle Dihydropyridine Receptor from Rana catesbeiana.
J. Zhou, L. Cribbs, J. Yi, R. Shirokov, E. Perez-Reyes, and E. Rios (1998)
J. Biol. Chem. 273, 25503-25509
   Abstract »    Full Text »    PDF »
Oxidation Regulates Cloned Neuronal Voltage-Dependent Ca2+ Channels Expressed in Xenopus Oocytes.
A. Li, J. Segui, S. H. Heinemann, and T. Hoshi (1998)
J. Neurosci. 18, 6740-6747
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Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
Y. Li-Smerin and K. J. Swartz (1998)
PNAS 95, 8585-8589
   Abstract »    Full Text »    PDF »
Physiological Features of Visceral Smooth Muscle Cells, With Special Reference to Receptors and Ion Channels.
H. KURIYAMA, K. KITAMURA, T. ITOH, and R. INOUE (1998)
Physiol Rev 78, 811-920
   Abstract »    Full Text »    PDF »
Isoform-Specific Inhibition of L-Type Calcium Channels by Dihydropyridines Is Independent of Isoform-Specific Gating Properties.
H. Hu and E. Marban (1998)
Mol. Pharmacol. 53, 902-907
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Modulation of human neuronal alpha 1E-type calcium channel by alpha 2delta -subunit.
N. Qin, R. Olcese, E. Stefani, and L. Birnbaumer (1998)
Am J Physiol Cell Physiol 274, C1324-C1331
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Pharmacological Characterization of the Human Ionotropic Glutamate Receptor Subtype GluR3 Stably Expressed in Mammalian Cells.
M. A. Varney, S. P. Rao, C. Jachec, C. Deal, S. D. Hess, L. P. Daggett, F.-F. Lin, E. C. Johnson, and G. Veliçelebi (1998)
J. Pharmacol. Exp. Ther. 285, 358-370
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Upregulation of L-Type Ca2+ Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia.
R. E. Westenbroek, S. B. Bausch, R. C. S. Lin, J. E. Franck, J. L. Noebels, and W. A. Catterall (1998)
J. Neurosci. 18, 2321-2334
   Abstract »    Full Text »    PDF »
A Mutation Affecting Dihydropyridine-Sensitive Current Levels and Activation Kinetics in Drosophila Muscle and Mammalian Heart Calcium Channels.
D. Ren, H. Xu, D. F. Eberl, M. Chopra, and L. M. Hall (1998)
J. Neurosci. 18, 2335-2341
   Abstract »    Full Text »    PDF »
Effects of 2,3-butanedione monoxime (BDM) on calcium channels expressed in Xenopus oocytes.
T J A Allen, G Mikala, X-P Wu, and A C Dolphin (1998)
J. Physiol. 508, 1-14
   Abstract »    Full Text »    PDF »
Familial Hemiplegic Migraine Mutations Change alpha 1A Ca2+ Channel Kinetics.
R. L. Kraus, M. J. Sinnegger, H. Glossmann, S. Hering, and J. Striessnig (1998)
J. Biol. Chem. 273, 5586-5590
   Abstract »    Full Text »    PDF »
Predominance of the alpha 1D subunit in L-type voltage-gated Ca2+ channels of hair cells in the chicken's cochlea.
R. Kollmar, L. G. Montgomery, J. Fak, L. J. Henry, and A. J. Hudspeth (1997)
PNAS 94, 14883-14888
   Abstract »    Full Text »    PDF »
Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-L-type Ca2+ channel.
G. H. Hockerman, B. Z. Peterson, E. Sharp, T. N. Tanada, T. Scheuer, and W. A. Catterall (1997)
PNAS 94, 14906-14911
   Abstract »    Full Text »    PDF »
Direct Inhibition of Expressed Cardiac L-Type Ca2+ Channels by S-Nitrosothiol Nitric Oxide Donors.
H. Hu Nipavan Chiamvimonvat Toshio Yamagishi Eduardo (1997)
Circ. Res. 81, 742-752
   Abstract »    Full Text »
Nine L-type Amino Acid Residues Confer Full 1,4-Dihydropyridine Sensitivity to the Neuronal Calcium Channel alpha 1A Subunit. ROLE OF L-TYPE MET1188.
M. J. Sinnegger, Z. Wang, M. Grabner, S. Hering, J. Striessnig, H. Glossmann, and J. Mitterdorfer (1997)
J. Biol. Chem. 272, 27686-27693
   Abstract »    Full Text »    PDF »
Molecular Studies on the Voltage Dependence of Dihydropyridine Action on L-type Ca2+ Channels. CRITICAL INVOLVEMENT OF TYROSINE RESIDUES IN MOTIF IIIS6 AND IVS6.
I. Bodi, H. Yamaguchi, M. Hara, M. He, A. Schwartz, and G. Varadi (1997)
J. Biol. Chem. 272, 24952-24960
   Abstract »    Full Text »    PDF »
Functional Expression and Characterization of Skeletal Muscle Dihydropyridine Receptors in Xenopus Oocytes.
D. Ren and L. M. Hall (1997)
J. Biol. Chem. 272, 22393-22396
   Abstract »    Full Text »    PDF »
Molecular Determinants of High Affinity Phenylalkylamine Block of L-type Calcium Channels in Transmembrane Segment IIIS6 and the Pore Region of the alpha 1 Subunit.
G. H. Hockerman, B. D. Johnson, M. R. Abbott, T. Scheuer, and W. A. Catterall (1997)
J. Biol. Chem. 272, 18759-18765
   Abstract »    Full Text »    PDF »
L-Type Calcium Channels in Insulin-Secreting Cells: Biochemical Characterization and Phosphorylation in RINm5F Cells.
H. Safayhi, H. Haase, U. Kramer, A. Bihlmayer, M. Roenfeldt, H. P.T. Ammon, M. Froschmayr, T. N. Cassidy, I. Morano, M. K. Ahlijanian, et al. (1997)
Mol. Endocrinol. 11, 619-629
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Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel alpha 1A subunit.
S. Herlitze, G. H. Hockerman, T. Scheuer, and W. A. Catterall (1997)
PNAS 94, 1512-1516
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Modulation of the Cloned Skeletal Muscle L-Type Ca2+ Channel by Anchored cAMP-Dependent Protein Kinase.
B. D. Johnson, J. P. Brousal, B. Z. Peterson, P. A. Gallombardo, G. H. Hockerman, Y. Lai, T. Scheuer, and W. A. Catterall (1997)
J. Neurosci. 17, 1243-1255
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Motif III S5 of L-type Calcium Channels Is Involved in the Dihydropyridine Binding Site. A COMBINED RADIOLIGAND BINDING AND ELECTROPHYSIOLOGICAL STUDY.
M. He, I. Bodi, G. Mikala, and A. Schwartz (1997)
J. Biol. Chem. 272, 2629-2633
   Abstract »    Full Text »    PDF »
Two Amino Acid Residues in the IIIS5 Segment of L-Type Calcium Channels Differentially Contribute to 1,4-Dihydropyridine Sensitivity.
J. Mitterdorfer, Z. Wang, M. J. Sinnegger, S. Hering, J. Striessnig, M. Grabner, and H. Glossmann (1996)
J. Biol. Chem. 271, 30330-30335
   Abstract »    Full Text »    PDF »
Transmembrane Auxiliary Subunits of Voltage-dependent Ion Channels.
C. A. Gurnett and K. P. Campbell (1996)
J. Biol. Chem. 271, 27975-27978
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Transfer of High Sensitivity for Benzothiazepines from L-type to Class A (BI) Calcium Channels.
S. Hering, S. Aczel, M. Grabner, F. Doring, S. Berjukow, J. Mitterdorfer, M. J. Sinnegger, J. Striessnig, V. E. Degtiar, Z. Wang, et al. (1996)
J. Biol. Chem. 271, 24471-24475
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Molecular Studies of the Asymmetric Pore Structure of the Human Cardiac Voltage- dependent Ca2+ Channel. CONSERVED RESIDUE, GLU-1086, REGULATES PROTON-DEPENDENT ION PERMEATION.
U. Klockner, G. Mikala, A. Schwartz, and G. Varadi (1996)
J. Biol. Chem. 271, 22293-22296
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Identification of Three Subunits of the High Affinity omega -Conotoxin MVIIC-sensitive Ca2+ Channel.
H. Liu, M. De Waard, V. E.S. Scott, C. A. Gurnett, V. A. Lennon, and K. P. Campbell (1996)
J. Biol. Chem. 271, 13804-13810
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Transfer of L-type Calcium Channel IVS6 Segment Increases Phenylalkylamine Sensitivity of alpha[IMAGE].
F. Döring, V. E. Degtiar, M. Grabner, Jör. Striessnig, S. Hering, and H. Glossmann (1996)
J. Biol. Chem. 271, 11745-11749
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Anti-Ig-induced Calcium Influx in Rat B Lymphocytes Mediated by cGMP through a Dihydropyridine-sensitive Channel.
A. A. Sadighi Akha, N. J. Willmott, K. Brickley, A. C. Dolphin, A. Galione, and S. V. Hunt (1996)
J. Biol. Chem. 271, 7297-7300
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Molecular Determinants of High Affinity Dihydropyridine Binding in L-type Calcium Channels.
B. Z. Peterson, T. N. Tanada, and W. A. Catterall (1996)
J. Biol. Chem. 271, 5293-5296
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The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the alpha(2)[IMAGE] Subunit of a Calcium Channel.
N. S. Gee, J. P. Brown, V. U. K. Dissanayake, J. Offord, R. Thurlow, and G. N. Woodruff (1996)
J. Biol. Chem. 271, 5768-5776
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Molecular Determinants of Cardiac Ca[IMAGE] Channel Pharmacology.
X. Wei, S. Pan, W. Lang, H. Kim, T. Schneider, E. Perez-Reyes, and L. Birnbaumer (1995)
J. Biol. Chem. 270, 27106-27111
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Regulation of Dihydropyridine and Ryanodine Receptor Gene Expression in Skeletal Muscle.
A. Ray, J. Kyselovic, J. J. Leddy, J. T. Wigle, B. J. Jasmin, and B. S. Tuana (1995)
J. Biol. Chem. 270, 25837-25844
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Molecular Determinants of High Affinity Phenylalkylamine Block of L-type Calcium Channels.
G. H. Hockerman, B. D. Johnson, T. Scheuer, and W. A. Catterall (1995)
J. Biol. Chem. 270, 22119-22122
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Calcium Binding in the Pore of L-type Calcium Channels Modulates High Affinity Dihydropyridine Binding.
B. Z. Peterson and W. A. Catterall (1995)
J. Biol. Chem. 270, 18201-18204
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Sites of Selective cAMP-dependent Phosphorylation of the L-type Calcium Channel [IMAGE]1 Subunit from Intact Rabbit Skeletal Muscle Myotubes.
E. I. Rotman, B. J. Murphy, and W. A. Catterall (1995)
J. Biol. Chem. 270, 16371-16377
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Co-localization of 1,4-dihydropyridine receptor alpha 2/delta subunit and N-CAM during early myogenesis in vitro.
S. Vandaele and F Rieger (1994)
J. Cell Sci. 107, 1217-1227
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Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel.
M. Williams, P. Brust, D. Feldman, S Patthi, S Simerson, A Maroufi, A. McCue, G Velicelebi, S. Ellis, and M. Harpold (1992)
Science 257, 389-395
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Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel.
L. Isom, K. De Jongh, D. Patton, B. Reber, J Offord, H Charbonneau, K Walsh, A. Goldin, and W. Catterall (1992)
Science 256, 839-842
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Functional subunit structure of voltage-gated calcium channels.
W. Catterall (1991)
Science 253, 1499-1500
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The roles of the subunits in the function of the calcium channel.
D Singer, M Biel, I Lotan, V Flockerzi, F Hofmann, and N Dascal (1991)
Science 253, 1553-1557
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