Abstract
This study reports a novel splice variant form of the voltage-dependent calcium channel β2 subunit (β2g). This variant is composed of the conserved amino-terminal sequences of the β2a subunit, but lacks the β-subunit interaction domain (BID), which is thought essential for interactions with the α1 subunit. Gene structure analysis revealed that this gene was composed of 13 translated exons spread over 107 kb of the genome. The gene structure of the β2 subunit was similar in exon-intron organization to the murine β3 and human β4 subunits. Electrophysiological evaluation revealed that β2a and β2g affected channel properties in different ways. The β2a subunit increased the peak amplitude, but failed to increase channel inactivation, while β2g had no significant effects on either the peak current amplitude or channel inactivation. Other β subunits, such as β3 and β4, significantly increased the peak current and accelerated current inactivation.
Similar content being viewed by others
References
Catterall WA: Structure and regulation of voltage-gated Ca2+ channels. Ann Rev Cell Dev Biol 16: 521-555, 2000
Lacerda AE, Kim HS, Ruth P, Perez-Reyes E, Flockerzi V, Hofmann F, Birnbauer F, Brown AM: Normalization of current kinetics by interaction between the α1 and β subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel. Nature 352: 527-530, 1991
Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N: Roles of the subunits of calcium channel in its expression and function. Science 253: 1553-1557, 1991
Neely A, Wei X, Olcese R, Birnbaumer L, Stefani E: 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, 1993
Birnbaumer L, Qin N, Olcese R, Tareilus E, Platano D, Costantin J, Stefani E: Structures and functions of calcium channel β subunits. J Bioenerg Biomembr 30: 357-375, 1998
Hullin R, Singer-Lahat D, Freichel M, Biel M, Dascal N, Hofmann F, Flockerzi V: Calcium channel β subunit heterogeneity: Functional expression of cloned cDNA from heart, aorta and brain. EMBO J 11: 885-890, 1992
Collin T, Lory P, Taviaux S, Courtieu C, Guilbault P, Berta P, Nargeot J: Cloning, chromosomal location and functional expression of the human voltage-dependent calcium-channel β3 subunit. Eur J Biochem 220: 257-262, 1994
DeWaard M, Pragnell M, Campbell KP: Ca2+ channel regulation by a conserved β subunit domain. Neuron 13: 495-503, 1994
Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, Mori Y, De Waard M: A new β subtype-specific interaction in α1A subunit controls P/Q-type Ca2+ channel activation. J Biol Chem 274: 12383-12390, 1999
Chien AJ, Carr KM, Shirokov RE, Rios E, Hosey MM: Membrane targeting of L-type calcium channels. J Biol Chem 274: 2137-2144, 1996
Qin N, Platano D, Olcese R, Costantin JL, Stefani E, Birnbaumer L: Unique regulatory properties of the type 2a Ca2+ channel β subunit caused by palmitoylation. Proc Natl Acad Sci USA 95: 4690-4695, 1998
Gao T, Chien AJ, Hosey MM: Complexes of the α1C and β subunits generate the necessary signal for membrane targeting of class C L-type calcium channels. J Biol Chem 274: 2137-2144, 1999
Castellano A, Perez-Reyes E: Molecular diversity of Ca2+ channel β subunits. Biochem Soc Trans 22: 483-488, 1994
Perez-Reyes E, Schneider T: Molecular biology of calcium channels. Kidney Int 48: 1111-1124, 1995
Bosse E, Bottlender R, Kleppisch T, Hescheler J, Welling A, Hofmann F, Flockerzi V: Stable and functional expression of the calcium channel α1 subunit from rabbit lung. EMBO J 11: 2033-2038, 1992
Welling A, Bosse E, Cavalié A, Bottlender B, Ludwig A, Nastainczyk W, Flockerzi V, Hofmann F: Stable co-expression of calcium channel α1, β and α2/δ subunits in a somatic cell line. J Physiol 471: 749-765, 1993
Murakami M, Wissenbach U, Flockerzi V: Gene structure of the murine calcium channel β3 subunit, cDNA and characterization of alternative splicing and transcription products. Eur J Biochem 236: 138-143, 1996
Burgess DL, Jones JM, Meisler MH, Noebels JL: Mutation of the Ca2+ channel β subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (l h) mouse. Cell 88: 385-392, 1997
Aoyama M, Murakami M, Iwashima T, Ito Y, Yamaki K, Nakayama S: Slow deactivation and U-shaped inactivation properties in cloned Cav1.2b channels in CHO cells. Biophys J 84: 709-724, 2003
Massa E, Kelly KM, Yule D, MacDonald RL, Uhler MD: Comparing of Fura-2 imaging and electrophysiological analysis of murine calcium channel α1 subunits coexpressed with novel β2 subunit isoforms. Mol Pharmacol 47: 707-716, 1995
Castellano A, Wei X, Birnbaumer L, Perez-Reyes E: Cloning and expression of a neuronal calcium channel β subunit. J Biol Chem 268: 3450-3455, 1993
Mermelstein PG, Foehring RC, Tkatch T, Song W-J, Baranauskas G, Surmeier DJ: Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression. J Neurosci 19: 7268-7277, 1999
Volsen SG, Day NC, McCormack AL, Smith W, Craig PJ, Beattie RE, Smith D, Ince PG, Shaw PJ, Ellis SB, Mayne N, Burnett, JP, Gillespie A, Harpold MM: The expression of voltage-dependent calcium channel β subunits in human cerebellum. Neuroscience 80: 161-174, 1997
Berrow NS, Campbell V, Fitzgerald EM, Brickley K, Dolphin AC: Antisense depletion of beta-subunits modulates the biophysical and pharmacological properties of neuronal calcium channels. J Physiol (Lond) 482: 481-491, 1995
Brice NL, Berrow NS, Campbell V, Page KM, Brickley K, Tedder I, Dolphin AC: Importance of the different β subunits in the membrane expression of the α1A and α2 calcium channel subunits: Studies using a depolarization-sensitive α1A antibody. Eur J Neurosci 9: 749-759, 1997
Escayg A, Jones JM, Kearney JA, Hitchcock PF, Meisler MH: Calcium channel β4 (CACNB4): Human ortholog of the mouse epilepsy gene lethargic. Genomics 50: 14-22, 1998
Olcese R, Qin N, Schneider T, Neely A, Wei X, Stefani E, Birnbaumer L: The amino terminus of a calcium channel β subunit sets rates of channel inactivation independently of the subunit's effect on activation. Neuron 13: 1433-1438, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Murakami, M., Aoyama, M., Suzuki, T. et al. Genetic characterization of a new splice variant of the β2 subunit of the voltage-dependent calcium channel. Mol Cell Biochem 254, 217–225 (2003). https://doi.org/10.1023/A:1027316017156
Issue Date:
DOI: https://doi.org/10.1023/A:1027316017156