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Structures and Functions of Calcium Channel β Subunits

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Abstract

Calcium channel β subunits have profound effects on how α1 subunits perform. In this article we summarize our present knowledge of the primary structures of β subunits as deduced from cDNAs and illustrate their different properties. Upon co-expression with α1 subunits, the effects of β subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have different responses to voltage which are affected by β subunits, such as long-lasting prepulse facilitation of α1C (absent in α1E) and inhibition by G protein βγ dimer of α1E, absent in α1C. One β subunit, a brain β2a splice variant that is palmitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of α1 in oocytes requires a β subunit even if the final channel shows no evidence for its presence. We propose two structural models for Ca2+ channels to account for “α1 alone” channels seen in cells with limited β subunit expression. In one model, β dissociates from the mature α1 after proper folding and membrane insertion. Regulated channels seen upon co-expression of high levels of β would then have subunit composition α1β. In the other model, the “chaperoning” β remains associated with the mature channel and “α1 alone” channels would in fact be α1β channels. Upon co-expression of high levels of β the regulated channels would have composition [α1β]β.

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REFERENCES

  • Artalejo, C. R., Mogul, D. J., Perlman, R. L., and Fox, A. P. (1991). “Three types of bovine chromaffin cell Ca2+ channels: facilitation increases the opening probability of a 27 pS channel.” J. Physiol. (London) 444, 213-40.

    Google Scholar 

  • Berrow, N. S., Campbell, V., Fitzgerald, E. M., Brickley, K., and Dolphin, A. C. (1995). “Antisense depletion of β-subunits modulates the biophysical and pharmacological properties of neuronal calcium channels.” J. Physiol. 482, 481-491.

    Google Scholar 

  • Beurg, M., Sukhareva, M., Strube, C., Powers, P. A., Gregg, R. G., and Coronado, R. (1997). “Recovery of Ca2+ current, charge movements, and Ca2+ transients in myotubes deficient in dihydropyridine receptor β1 subunit transfected with β1 cDNA.” Biophys. J. 73, 807-818.

    Google Scholar 

  • Bourinet, E., Charnet, P., Tomlinson, W. J., Stea, A., Snutch, T. P., and Nargeot, J. (1994). “Voltage-dependent facilitation of a neuronal α1C L-type calcium channel.” EMBO J. 13, 5032-5039.

    Google Scholar 

  • Bourinet, E., Zamponi, G. W., Stea, A., Soong, T. W., Lewis, B. A., Jones, L. P., Yue, D. T., and Snutch, T. P. (1996). “The α1E calcium channel exhibits permeation properties similar to low-voltage-activated calcium channels,” J. Neurosci. 16, 4983-4993.

    Google Scholar 

  • Brown, H. F., Kimura, J., Noble, D., Noble, S. J., and Taupignon, A. (1984a). “The slow inward current, isi, in the rabbit sinoatrial node investigated by voltage clamp and computer simulation,” Proc. Roy. Soc. London. Ser. B: Biol. Sci. 222, 305-328.

    Google Scholar 

  • Brown, H. F., Kimura, J., Noble, D., Noble, S. J., and Taupignon, A. (1984b). “The ionic currents underlying pacemaker activity in rabbit sino-atrial node: experimental results and computer simulations.” Proc. Roy. Soc. London. Ser. B: Biol. Sci. 222, 329-347.

    Google Scholar 

  • Burgess, D. L., Jones, J. M., Meisler, M. H., and Noebels, J. L. (1997). “Mutation of the Ca2+ channel β subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse,” Cell 88, 385-392

    Google Scholar 

  • Campbell, V., Berrow, N. S., Fitzgerald, E. M., Brickley, K., and Dolphin, A. C. (1995). “Inhibition of the interaction of G protein Go with calcium channels by the calcium channel β-subunit in rat neurones,” J. Physiol. 485, 365-372.

    Google Scholar 

  • Castellano, A., Wei, X., Birnbaumer, L., and Perez-Reyes, E. (1993a). “Cloning and expression of a third calcium channel β subunit,” J. Biol. Chem. 268, 3450-3455.

    Google Scholar 

  • Castellano, A., Wei, X., Birnbaumer, L., and Perez-Reyes, E. (1993b). “Cloning and expression of a neuronal calcium channel β Subunit,” J. Biol. Chem. 268, 12359-12366.

    Google Scholar 

  • Cens T., Mangoni M. E., Richard S., Nargeot J., and Charnet P. (1996). “Coexpression of the β2 subunit does not induce voltage-dependent facilitation of the class C L-type Ca channel,” Pflugers Arch. 431, 771-774.

    Google Scholar 

  • Chang, C. F., Gutierrez, L. M., Mundina-Weilenmann, C., and Hosey M. M. (1991). “Dihydropyridine-sensitive calcium channels from skeletal muscle. II. Functional effects of differential phosphorylation of channel subunits,” J. Biol. Chem. 266, 16395-16400.

    Google Scholar 

  • Chien, A. J., Zhao, X., Shirokov, R. E., Puri, T. S., Chang, C. F., Sun, D., Rios, E., and Hosey, M. M. (1995). “Roles of a membrane-localized β subunit in the formation and targeting of functional L-type Ca2+ channels,” J. Biol. Chem. 270, 30036-30044.

    Google Scholar 

  • Chien, A. J., Carr, K. M., Shirokov, R. E., Rios, E. and Hosey, M. M. (1996). “Identification of palmitoylation sites within the L-type calcium channel β2a subunit and effects on channel function,” J. Biol. Chem. 271, 26465-26468.

    Google Scholar 

  • Chin, H., Kwon, O. J., Jung, H. H., Kim, D. S., and Kozak, C. A. (1995). “Genetic mapping of the mouse genes encoding the voltage-sensitive calcium channel subunits,” Genomics 28, 592-599.

    Google Scholar 

  • Collin, T., Wang, J.-J., Nargeot, J., and Schwartz, A. (1993). “Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel β subunit from normal human heart,” Circ. Res. 72, 1337-1344.

    Google Scholar 

  • Collin, T., Lory, P., Taviaux, S., Courtieu, C., Guilbault, P., Berta, P., and Nargeot, J. (1994). “Cloning, chromosomal location and functional expression of the human voltage-dependent calcium-channel β3 subunit,” Eur. J. Biochem. 220, 257-262.

    Google Scholar 

  • Curtis, B. M., and Catterall, W. A. (1984). “Purification of the calcium antagonist receptor of the voltage-sensitive calcium channel from skeletal muscle transverse tubules,” Biochemistry 23, 2113-2118.

    Google Scholar 

  • De Jongh, K. S., Merrick, D. K., and Catterall, W. A. (1989). “Subunits of purified calcium channels: a 212-kDa form of α1 partial amino acid sequence of a phosphorylation site of an independent β subunit,” Proc. Natl. Acad. Sci. USA 86, 8585-8589.

    Google Scholar 

  • DeJongh, K. S., Warner, C., and Catterall, W. A. (1990). “Subunits of purified calcium channels. α2 and δ are encoded by the same gene,” J. Biol. Chem. 265, 14738-14741.

    Google Scholar 

  • De Waard, M. D., Pragnell, M., and Campbell, K. P. (1994). “Ca channel regulation by a conserved β subunit domain,” Neuron 13, 495-503.

    Google Scholar 

  • Dolphin, A. C. (1996). “Facilitation of Ca2+ currents in excitable cells,” Trends Neurosci. 19, 35-43.

    Google Scholar 

  • Dunlap, K., and Fischbach, G. D. (1981). “Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones.” J. Physiol. 317, 519-535.

    Google Scholar 

  • Ellinor, P. T., Zhang, J.-F., Randall, A. D., Zhou, M., Schwarz, T. L., Tsien, R. W., and Horne, W. A. (1993). “Functional expression of a rapidly inactivating neuronal calcium channel.” Nature 363, 455-458.

    Google Scholar 

  • Fedida D., Noble D., and Spindler A. J. (1988). “Mechanism of the use dependence of Ca2+ current in guinea-pig myocytes.” J. Physiol. (London) 405, 461-475.

    Google Scholar 

  • Flockerzi, V., Oeken, H.-J., Hofmann, F., Pelzer, D., Cavalie, A., and Trautwein, W. (1986). “Purified dihydropyridine-binding site from skeletal muscle T-tubules is a functional calcium channel,” Nature 323, 66-68.

    Google Scholar 

  • Grabner, M., Wang, Z., Mitterdorfer, J., Rosenthal, F., Charnet, P., Savchenko, A., Hering, S., Ren, D., Hall, L. M., and Glossmann, H. (1994). “Cloning and functional expression of a neuronal calcium channel beta subunit from housefly Musca domestica.” J. Biol. Chem. 269, 23668-23674.

    Google Scholar 

  • Gregg, R. G., Powers, P. A., and Hogan, K. (1993). “Assignment of the human gene for the β subunit of the voltage-dependent calcium channel (CACNLB1) to chromosome 17 using somatic cell hybrids and linkage mapping,” Genomics 15, 185-187.

    Google Scholar 

  • Gregg, R. G., Messing, A., Strube, C., Beurg, M., Moss, R., Behan, M., Sukhareva, M., Haynes, S., Powell, J. A., and Coronado, R. (1996). “Absence of the β subunit (CCHβ1) of the skeletal muscle dihydropyridine receptor alters expression of the α1 subunit and eliminates excitation-contraction coupling,” Proc. Natl. Acad. Sci. U.S.A. 93, 13961-13966.

    Google Scholar 

  • Gutierrez, L. M., Zhao, X. L., and Hosey, M. M. (1994). “Protein kinase C-mediated regulation of L-type Ca channels from skeletal muscle requires phosphorylation of the α1 subunit,” Biochem. Biophys. Res. Commun. 202, 857-865.

    Google Scholar 

  • Haase, H., Bartel, S., Karczewski, P., Morano, I., and Krause, E. G. (1996). “In vivo phosphorylation of the cardiac L-type calcium channel β-subunit in response to catecholamines,” Mol. Cell. Biochem. 163–164, 99-106.

    Google Scholar 

  • Hancock, J. F., Magee, A. I., Childs, J. E., and Marshall, C. J. (1989). “All ras proteins are polyisoprenylated but only some are palmitoylated,” Cell 57, 1167-1177.

    Google Scholar 

  • Herlitze, S., Garcia, D. E., Mackie, K., Hille, B., Scheuer, T. and Catterall, W. A. (1996) “Modulation of Ca2+ Channels by G-Protein βγ Subunits,” Nature 380, 258-262.

    Google Scholar 

  • Hullin, R., Singer-Lahat, D., Freichel, M., Biel, M., Dascal, N., Hofmann, F., and Flockerzi, V. (1992). “Calcium channel β subunit heterogeneity: Functional expression of cloned cDNA from heart, aorta and brain,” EMBO J. 11, 885-890.

    Google Scholar 

  • Ikeda, S. R. (1991). “Double-pulse calcium channel current facilitation in adult rat sympathetic neurones,” J. Physiol. (London) 439, 181-214.

    Google Scholar 

  • Ikeda S. R. (1996). “Voltage-dependent modulation of N-type calcium channels by G protein βγ subunits,” Nature 380, 255-258.

    Google Scholar 

  • Iles, D. E., Segers, B., Sengers, R. C., Monsieurs, K., Heytens, L., Halsall, P. J., Hopkins P. M., Ellis, F. R., Hall-Curran, J. L., Stewart, A. D., et al. (1993). “Genetic mapping of the βl-and γ-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility,” Hum. Mol. Genet. 2, 863-868.

    Google Scholar 

  • Kavalali, E. T., and Plummer, M. R. (1996). “Multiple voltage-dependent mechanisms potentiate calcium channel activity in hippocampal neurons,” J. Neurosci. 16, 1072-1082.

    Google Scholar 

  • Kleppisch, T., Pedersen, K., Strubing, C., Bosse-Doenecke, E., Flockerzi, V., Hofmann, F., and Hescheler, J. (1994). Double-pulse facilitation of smooth muscle alpha l-subunit Ca2+ channels expressed in CHO cells, Embo J. 13, 2502-7.

    Google Scholar 

  • Lacerda, A. E., Kim, H., Ruth, P., Perez-Reyes, E., Flockerzi, V., Hofmann, F., Birnbaumer, L., and Brown, A. M. (1991). “Normalization of current kinetics by interaction between the α1 and β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel,” Nature 352, 527-530.

    Google Scholar 

  • Lacerda, A. E., Perez-Reyes, E., Wei, X., Castellano, A., and Brown, A. M. (1994). “T-and N-type calcium channels in Xenopus oocytes. Evidence for specific interactions with β subunits,” Biophys. J. 66, 1833-1843.

    Google Scholar 

  • Lee, K. S. (1987). “Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization,” Proc. Natl. Acad. Sci. USA 84, 3941-3945.

    Google Scholar 

  • Mori, Y., Friedrich, T., Kim, M.-S., Mikami, A., Nakai, J., Ruth, P., Bosse, E., Hofmann, F., Flockerzi, V., Furuichi, T., Mikoshiba, K., Imoto, K., Tanabe, T., and Numa, S. (1991). “Primary structure and functional expression from complementary DNA of a brain calcium channel,” Nature 350, 398-402.

    Google Scholar 

  • Murakami, M., Wissenbach, U., and Flockerzi, V. (1996). “Gene structure of the murine calcium channel β3 subunit, cDNA and characterization of alternative splicing and transcription products,” Eur. J. Biochem. 236, 138-143.

    Google Scholar 

  • Neely, A., Wei, X., Olcese, R., Birnbaumer, L., and Stefani, E. (1993). “Potentiation by the β subunit of the ratio of the ionic current to the charge movement in the cardiac calcium channel,” Science 262, 575-578.

    Google Scholar 

  • Neely, A., Olcese, R., Baldelli, P., Wei, X., Birnbaumer, L., and Stefani, E. (1995). “Dual activation of the cardiac Ca2+ channel α1c subunit and its modulation by the β subunit,” Am. J. Physiol. 268, C732-C740.

    Google Scholar 

  • Noble, S., and Shimoni, Y. (1981a). “The calcium and frequency dependence of the slow inward current ‘staircase’ in frog atrium,” J. Physiol. (London) 310, 57-75.

    Google Scholar 

  • Noble, S., and Shimoni, Y. (1981b). “Voltage-dependent potentiation of the slow inward current in frog atrium,” J. Physiol. (London) 310, 77-95.

    Google Scholar 

  • Noceti, F., Baldelli, P., Wei, X., Qin, N., Toro, L., Birnbaumer, L., and Stefani, E. (1996). “Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels,” J. Gen. Physiol. 108, 143-156.

    Google Scholar 

  • Olcese, R., Qin, N., Neely, A., Wei, X., Stefani, E., and Birnbaumer, L. (1994). “The amino terminus of a calcium channel β subunit sets rates of channel inactivation independently of the subunit's effects on activation,” Neuron 13, 1433-1438.

    Google Scholar 

  • Olcese, R., Neely, A., Qin, N., Wei, X., Birnbaumer, L., and Stefani, E. (1996). “Coupling between charge movement and pore opening in vertebrate neuronal α1E calcium channels,” J. Physiol. 497, 675-686.

    Google Scholar 

  • Osterrieder, W., Brum, G., Hescheler, J., Trautwein, W., Flockerzi, V., and Hofmann, F. (1982). “Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current,” Nature 298, 576-578.

    Google Scholar 

  • Park, S. H., Suh, Y. S., Kim, H., Rhyu, I. J., and Kim, H. L. (1997). “Chromosomal localization and neural distribution of voltage-dependent calcium channel β3 subunit gene,” Molecules & Cells 7, 200-203.

    Google Scholar 

  • Perez-Reyes, E., Castellano, A., Kim, H. S., Bertrand, P., Baggstrom, E., Lacerda, A. E., Wei, X., and Birnbaumer, L. (1992). “Cloning and expression of a cardiac/brain β subunit of the L-type calcium channel,” J. Biol. Chem. 267, 1792-1797.

    Google Scholar 

  • Powers, P. A., Liu, S., Hogan, K., and Gregg, R. G. (1992). “Skeletal muscle and brain isoforms of a β-subunit of human voltage-dependent calcium channels are encoded by a single gene, J. Biol. Chem. 267, 22967-22972.

    Google Scholar 

  • Pragnell, M., Sakamoto, J., Jay, S. D., and Campbell, K. P. (1991). “Cloning and tissue-specific expression of the brain calcium channel beta-subunit,” FEBS Lett. 291, 253-258.

    Google Scholar 

  • Pragnell, M., De Waard, M., Mori, Y., Tanabe, T., Snutch, T., and Campbell, K. P. (1994). “Calcium channel β-subunit binds to a conserved motif of the I–II cytoplasmic linker of the α1-subunit,” Nature 368, 67-70.

    Google Scholar 

  • Qin, N., Olcese, R., Zhou, J., Cabello, O., Birnbaumer, L., and Stefani, E. (1996). “Identification of a second region of the β subunit involved in regulation of calcium channel inactivation,” Am. J. Physiol. 271, C1539-C1545.

    Google Scholar 

  • Qin, N., Platano, D., Olcese, R., Stefani, E., and Birnbaumer, L. (1997). “Direct interaction of Gβγ with a novel C-terminal Gβγ binding domain of α1 is responsible for inhibition of presynaptic Ca2+ channels by G protein-coupled receptors,” Proc. Natl. Acad. Sci. USA 94, 8866-8871.

    Google Scholar 

  • Ruth, P., Röhrkasten, A., Biel, M., Bosse, E., Regulla, S., Meyer, H. E., Flockerzi, V., and Hofmann, F. (1989). “Primary structure of the β subunit of the DHP-sensitive calcium channel from skeletal muscle,” Science 245, 1115-1118.

    Google Scholar 

  • Schneider, T., Wei, X., Olcese, R., Costantin, J., Neely, A., Palade, P., Perez-Reyes, E., Qin, N., Zhou, J., Crawford, G. D., Smith, G. R., Appel, S. H., Stefani, E., and Birnbaumer, L. (1994). “Molecular analysis and functional expression of the human type E neuronal Ca2+ channel α1 subunit,” Receptors & Channels 2, 255-270.

    Google Scholar 

  • Singer, D., Biel, M., Lotan, I., Flockerzi, V., Hofmann, F., and Dascal, N. (1991). “The roles of the subunits in the function of the calcium channel,” Science 253, 1553-1557.

    Google Scholar 

  • Soong, T. W., Stea, A., Hodson, C. D., Dubel, S. J., Vincent, S. R., and Snutch, T. P. (1993). “Structure and functional expression of a member of a low voltage activated calcium channel family,” Science 260, 1133-1136.

    Google Scholar 

  • Stea, A., Tomlinson, W. J., Soong, T. W., Bourinet, E., Dubel, S. J., Vincent, S. R., and Snutch, T. P. (1994). “Localization and functional properties of a rat brain α1A calcium channel reflect similarities to neuronal Q-and P-type channels,” Proc. Natl. Acad. Sci. USA 91, 10576-10580.

    Google Scholar 

  • Strube, C., Beurg, M., Powers, P. A., Gregg, R. G., and Coronado, R. (1996). “Reduced Ca2+ current, change movement, and absence of Ca2+ transients in skeletal muscle deficient in dihydropyridine receptor β1 subunit,” Biophys. J. 71, 2531-2543.

    Google Scholar 

  • Taglialatela, M., Toro, L., and Stefani, E. (1992). “Novel voltage clamp to record small, fast currents from ion channels expressed in Xenopus oocytes,” Biophys. J. 61, 78-82.

    Google Scholar 

  • Tareilus, E., Roux, M., Qin, N., Olcese, R., Zou, J., Stefani, E., and Birnbaumer, L. (1997). “A Xenopus oocyte β subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit,” Proc. Natl. Acad. Sci. USA 94, 1703-1708.

    Google Scholar 

  • Taviaux, S., Williams, M. E., Harpold, M. M., Nargeot, J., and Lory, P. (1997). “Assignment of human genes for β2 and β4 subunits of voltage-dependent Ca2+ channels to chromosomes 10p12 and 2q22–q23,” Hum. Genet. 100, 151-154.

    Google Scholar 

  • Tsunoo, A., Yoshi, M., and Narahashi, T. (1986). “Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells,” Proc. Natl. Acad. Sci. USA 83, 9832-9836.

    Google Scholar 

  • Wei, X., Perez-Reyes, E., Lacerda, A. E., Schuster, G., Birnbaumer, L., and Brown, A. M. (1991). “Heterologous regulation of the cardiac calcium channel α1 subunit by skeletal muscle β and γ subunits. Implications for the structure of cardiac L-type calcium channels,” J. Biol. Chem. 266, 21943-21947.

    Google Scholar 

  • Wei, X., Neely, A., Olcese, R., Stefani, E., and Birnbaumer, L. (1996). “Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac α1C subunit,” Receptors & Channels 4, 205-215.

    Google Scholar 

  • Williams, M. E., Feldman, D. H., McCue, A. F., Brenner, R., Velicelebi, G., Ellis, S. B., and Harpold, M. M. (1992). “Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype,” Neuron 8, 71-84.

    Google Scholar 

  • Witcher, D. R., De Waard, M., Liu, H., Pragnell, M., and Campbell K. P. (1995). “Association of native Ca2+ channel β subunits with the α1 subunit interaction domain,” J. Biol. Chem. 270, 18088-18093.

    Google Scholar 

  • Yatani, A., Wakamori, M., Niidome, T., Yamamoto, S., Tanaka, I., Mori, Y., Katayama, K., and Green, S. (1995). “Stable expression and coupling of cardiac L-type Ca2+ channels with β1-adrenoceptors.” Circulation Research 76, 335-342.

    Google Scholar 

  • Zamponi, G. W., Bourinet, E., and Snutch, T. P. (1996). “Nickel block of a family of neuronal calcium channels: subtype-and subunit-dependent action at multiple sites,” J. Membr. Biol. 151, 77-90.

    Google Scholar 

  • Zhang, J. F., Ellinor, P. T., Aldrich, R. W., and Tsien, R. W. (1996). “Multiple structural elements in voltage-dependent calcium channels support their inhibition by G proteins,” Neuron 17, 991-1003.

    Google Scholar 

  • Zygmunt, A. C., and Maylie, J. (1990). “Stimulation-dependent facilitation of the high threshold calcium current in guineapig ventricular myocytes,” J. Physiol. (London) 428, 653-671.

    Google Scholar 

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Authors
  1. Lutz Birnbaumer
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  2. Ning Qin
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  3. Riccardo Olcese
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  4. Erwin Tareilus
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  5. Daniela Platano
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  6. Jim Costantin
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  7. Enrico Stefani
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Birnbaumer, L., Qin, N., Olcese, R. et al. Structures and Functions of Calcium Channel β Subunits. J Bioenerg Biomembr 30, 357–375 (1998). https://doi.org/10.1023/A:1021989622656

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