Differential Effects of Ca2+ Channel β1a and β2a Subunits on Complex Formation with α1S and on Current Expression in tsA201 Cells

Abstract

To study the interactions of the α1S subunit of the skeletal musclel-type Ca2+ channel with the skeletal β1a and the cardiac β2a, these subunits were expressed alone or in combination in tsA201 cells. Immunofluorescence- and green fluorescent protein-labeling showed that, when expressed alone, β1a was diffusely distributed throughout the cytoplasm, β2a was localized in the plasma membrane, and α1S was concentrated in a tubular/reticular membrane system, presumably the endoplasmic reticulum (ER). Upon coexpression with α1S, β1a became colocalized with α1S in the ER. Upon coexpression with β2a, α1S redistributed to the plasma membrane, where it aggregated in large clusters. Coexpression of α1S with β1a but not with β2aincreased the frequency at which cells expressed l-type currents. A point mutation (α1S-Y366S) or deletion (α1S-Δ351–380) in the β interaction domain of α1S blocked both translocation of β1a to the ER and β2a-induced translocation of the α1S mutants to the plasma membrane. However, the point mutation did not interfere with β1a-induced current stimulation. Thus, β1a and β2a are differentially distributed in tsA201 cells and upon coexpression with α1S, form α1S·β complexes in different cellular compartments. Complex formation but not current stimulation requires the intact β interaction domain in the I-II cytoplasmic loop of α1S. To study the interactions of the α1S subunit of the skeletal musclel-type Ca2+ channel with the skeletal β1a and the cardiac β2a, these subunits were expressed alone or in combination in tsA201 cells. Immunofluorescence- and green fluorescent protein-labeling showed that, when expressed alone, β1a was diffusely distributed throughout the cytoplasm, β2a was localized in the plasma membrane, and α1S was concentrated in a tubular/reticular membrane system, presumably the endoplasmic reticulum (ER). Upon coexpression with α1S, β1a became colocalized with α1S in the ER. Upon coexpression with β2a, α1S redistributed to the plasma membrane, where it aggregated in large clusters. Coexpression of α1S with β1a but not with β2aincreased the frequency at which cells expressed l-type currents. A point mutation (α1S-Y366S) or deletion (α1S-Δ351–380) in the β interaction domain of α1S blocked both translocation of β1a to the ER and β2a-induced translocation of the α1S mutants to the plasma membrane. However, the point mutation did not interfere with β1a-induced current stimulation. Thus, β1a and β2a are differentially distributed in tsA201 cells and upon coexpression with α1S, form α1S·β complexes in different cellular compartments. Complex formation but not current stimulation requires the intact β interaction domain in the I-II cytoplasmic loop of α1S. Voltage-activated Ca2+ channels are expressed in a multitude of tissues and are involved in a variety of cell functions (1Catterall W.A. Annu. Rev. Biochem. 1995; 64: 493-531Crossref PubMed Scopus (777) Google Scholar). The skeletal muscle l-type Ca2+ channel, also called dihydropyridine (DHP) 1The abbreviations used are: DHP, dihydropyridine; GFP, green fluorescent protein; βGFP, fusion protein of β1a and GFP; nt, nucleotide; ER, endoplasmic reticulum. receptor, is localized in the junctions between the transverse tubules and the sarcoplasmic reticulum (2Jorgensen A.O. Shen A.C.-Y. Arnold W. Leung A.T. Campbell K.P. J. Cell Biol. 1989; 109: 135-147Crossref PubMed Scopus (83) Google Scholar, 3Flucher B.E. Morton M.E. Froehner S.C. Daniels M.P. Neuron. 1990; 5: 339-351Abstract Full Text PDF PubMed Scopus (72) Google Scholar), where it primarily functions as the voltage sensor in excitation-contraction coupling (4Rios E. Ma J. Gonzales A. J. Muscle Res. Cell Motil. 1991; 12: 127-135Crossref PubMed Scopus (128) Google Scholar, 5Melzer W. Herrmann-Frank A. Lüttgau H.C. Biochim. Biophys. Acta. 1995; 1241: 59-116Crossref PubMed Scopus (484) Google Scholar). It consists of five subunits: the pore-forming α1S subunit, the α2δ subunit complex, a peripheral membrane protein, the β1asubunit, and the γ subunit, which is unique for this tissue (6Takahashi M. Seagar M.J. Jones J.F. Reber B.F. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1987; 84: 5478-5482Crossref PubMed Scopus (328) Google Scholar, 7Leung A.T. Imagawa T. Campbell K.P. J. Biol. Chem. 1987; 262: 7943-7946Abstract Full Text PDF PubMed Google Scholar, 8Vaghy P.L. Striessnig J. Miwa K. Knaus H.-G. Itagaki K. McKenna E. Glossmann H. Schwartz A. J. Biol. Chem. 1987; 262: 14337-14342Abstract Full Text PDF PubMed Google Scholar). Besides functioning as the ion channel proper, the α1Ssubunit contains the binding sites for specific drugs (9Striessnig J. Glossmann H. Catterall W.A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 9108-9112Crossref PubMed Scopus (139) Google Scholar, 10Hockerman G.H. Johnson B.D. Scheuer T. Catterall W.A. J. Biol. Chem. 1995; 270: 22119-22122Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar) and domains for interactions with the Ca2+ release channel (11Tanabe T. Beam K.G. Adams B.A. Niidome T. Numa S. Nature. 1990; 346: 567-569Crossref PubMed Scopus (492) Google Scholar) and the accessory channel subunits (12Pragnell M. De Waard M. Mori Y. Tanabe T. Snutch T.P. Campbell K.P. Nature. 1994; 368: 67-70Crossref PubMed Scopus (552) Google Scholar). The molecular domain responsible for binding the β subunit is a conserved motif of nine amino acids in the cytoplasmic loop between repeats I and II of the α1 subunit. Mutations within this motif severely interfered with β binding to α1 and with β-induced current stimulation (13De Waard M. Scott V.E.S. Pragnell M. Campbell K.P. FEBS Lett. 1996; 380: 272-276Crossref PubMed Scopus (82) Google Scholar). The β subunit exists in several isoforms and splice variants in different tissues Catterall W.A. Neuron. 1994; 12: Full Text PDF PubMed Scopus Google Scholar). Coexpression of of α1 subunits and accessory subunits in of the functions of the the α1 subunit alone is for the of A. K. Tanabe T. Niidome T. Mori Y. H. S. Numa S. Nature. 1989; Scopus Google Scholar, E. W. Campbell K.P. Nature. 1989; PubMed Scopus Google Scholar), of α2δ and β subunits the of channels the plasma membrane and the current E. Nature. 1991; PubMed Scopus Google Scholar, M. Schwartz A. Nature. 1991; PubMed Scopus Google Scholar, Schwartz A. Biophys. J. Full Text PDF PubMed Scopus Google Scholar). β coexpression to the Ca2+ and binding of J. M. M. Striessnig J. Glossmann H. FEBS Lett. 1994; PubMed Scopus Google Scholar), to current and Biophys. J. 1996; Full Text PDF PubMed Scopus (72) Google Scholar). A multitude of of β Ca2+ However, are as as the subunit and used for these Catterall W.A. Neuron. 1994; 12: Full Text PDF PubMed Scopus Google Scholar, M. Annu. Rev. 1994; PubMed Scopus Google Scholar). The for of current β are the in in of with β2a M. Schwartz A. A. Biochem. Biophys. Res. PubMed Scopus Google Scholar, E. T. T. M. J. 1995; PubMed Scopus (128) Google Scholar) and in a of current but not of upon coexpression of with a E. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). for of coupling A. E. 262: PubMed Scopus Google Scholar) and a of Ca2+ sites in the channel J. M. M. Striessnig J. Glossmann H. FEBS Lett. 1994; PubMed Scopus Google Scholar). several the which β channel in the plasma membrane it was with the cardiac β2a subunit is localized in the plasma membrane and coexpression of the cardiac with β2a the translocation of the membrane E. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). A translocation of a subunit the plasma membrane was different β β2a, and Campbell K. J. PubMed Scopus Google Scholar). not of the β subunits are to translocation were localized in the plasma membrane. and β2a but not and showed a plasma membrane at is a which β2a to the plasma membrane. However, mutation of these blocked of β2a expressed in tsA201 cells a of current stimulation but not of channel as in of E. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). The skeletal muscle l-type Ca2+ channel is Ca2+ channels with to in the B.E. Proc. Natl. Acad. Sci. U. S. A. 1996; PubMed Scopus Google Scholar), with to in excitation-contraction coupling (4Rios E. Ma J. Gonzales A. J. Muscle Res. Cell Motil. 1991; 12: 127-135Crossref PubMed Scopus (128) Google Scholar), and with to of channel Catterall W.A. Neuron. 1994; 12: Full Text PDF PubMed Scopus Google Scholar, B.D. G.H. Y. Scheuer T. Catterall W.A. J. PubMed Google Scholar). interactions between the skeletal muscle α1 and β subunits expressed in cells also of isoforms is not of β1a and β2a the and current stimulation upon coexpression with α1S in tsA201 cells. A mutation in the β interaction domain of α1S with the of the subunits but not with the β1a-induced stimulation of Ca2+ currents. tsA201 a cell with the large were and in were to fluorescent protein and cells were at of and the when cells cells were in at a of at cells were at between and to cells for the were with a to the The of used was of which was specific α1S and the was with J. T. J. Scopus Google Scholar). or were at in coexpression of with α1S in of cells. The was in of and to the the the cells were for or for The of the was the T. Beam K.G. Numa S. Nature. PubMed Scopus Google Scholar) and the Mutations were α1S of the the 1989; PubMed Scopus Google Scholar). a a of of of the was the the a the in the α1S were different the for a in the α1S in to the for a deletion mutation in the α1S to and the for deletion mutation in the α1S to To the of a of was a mutation in the The α1S were the with and were The of a fusion protein five the the was the a of and of and the the of of of the J. M. M. Striessnig J. Glossmann H. FEBS Lett. 1994; PubMed Scopus Google Scholar) was the the a of the of the to the of the was the fusion the of and of of the the the and the was the of and of The of the was were as B.E. S. J. Cell Biol. PubMed Scopus Google Scholar). with GFP, were used to between the and the green and the of are in were a with and and and The were for in in B.E. S. J. Cell Biol. PubMed Scopus Google Scholar, B.E. J. Cell Biol. 1991; PubMed Scopus Google Scholar, B.E. Daniels M.P. Biol. 1994; 5: PubMed Scopus Google Scholar). the of and with were skeletal muscle T. Beam K.G. Numa S. Nature. PubMed Scopus Google to deletion of amino acids deletion of amino acids skeletal muscle A. M. E. S. 1989; PubMed Scopus Google fusion fluorescent Nature. 1995; PubMed Scopus Google E. A. E. J. Biol. Chem. Full Text PDF PubMed Google J. T. J. Scopus Google in a receptor, M.E. Froehner S.C. J. Cell Biol. 1987; 262: receptor, M. H. Striessnig J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in a were the of the A. E. J. PubMed Scopus Google Scholar). were in a and with a a cells or were for for with cells. The and to and were with and to with of the were between and the was used for were the was for in the was were with and at with To cells for the of a voltage was used to a of current these the current in the current was tsA201 cells or cells with showed in of currents. with the current at the voltage and with for a current at also S. M. M. Glossmann H. S. J. 1996; PubMed Scopus Google Scholar). To a with the of the expressed current was the cells with the α1S showed with the current between and of the voltage were to the of of the α1S a were for cells with a current a voltage with a of and of in to a The and current at and α1S showed when α1S and in M. Schwartz A. Nature. 1991; PubMed Scopus Google Scholar) or in M. Biophys. J. 1996; Full Text PDF PubMed Scopus Google Scholar). a fusion protein of the β1a subunit of the skeletal muscle and GFP, called βGFP, as a for the of β1a expressed in tsA201 cells. in the of cells the β1a subunit and of tsA201 cells with and the β subunit in of both a and with the fusion protein or with the β1a also in β Thus, a of the and the fusion protein of the was when the β was upon coexpression with the α1S subunit showed of and β1a Ca2+ were in in which the cardiac was with or β1a U. and E. and upon coexpression of both β with α1S in skeletal U. Glossmann H. Tanabe T. B.E. Proc. Natl. Acad. Sci. U. S. A. Google Scholar). Thus, used in of with the of the of β1a and in cells. The of when expressed in tsA201 cells was and distributed throughout the The did not to with membrane or cytoplasmic the and the was different the alone, which was also diffusely distributed throughout the but in the The α1S subunit of the expressed in tsA201 cells showed a different α1S with a specific showed it was in a of a membrane throughout the and The tubular/reticular was in the and the was also The of the in of the cells. these the is as the ER. cytoplasmic the plasma membrane, were not with the of tsA201 cells with in which the β interaction domain or showed the in the ER and expressed alone was diffusely distributed throughout the a and However, when was with the α1S subunit of the receptor, the became localized in the tubular/reticular membrane system, presumably the ER and The was of and of the plasma membrane of and α1S showed a of β1a and α1S in the ER a and To this of was to with the α1S subunit, α1S with in the β interaction domain the β interaction domain in the of the β interaction domain in in with in the β interaction domain of to binding of and current stimulation (12Pragnell M. De Waard M. Mori Y. Tanabe T. Snutch T.P. Campbell K.P. Nature. 1994; 368: 67-70Crossref PubMed Scopus (552) Google Scholar). the translocation of the to the ER was a of a of β1a to α1S, in the β interaction domain of α1S the translocation of of the of β1a and α1S in tsA201 cells with the and α1S is with and α1S is with and α1S are colocalized in a cytoplasmic membrane and and are both localized in the membrane in these cells is not with the membrane but diffusely distributed in the and a of a of the cell at when was with the in which the β interaction domain the was and of expressed alone and of the when expressed alone or in combination with of the α1S mutants showed of cells with α1S a ER of βGFP, but in of the cells with or was in the ER The of cells in did not ER of cells expressed and not α1S and cells with The of upon coexpression with the different was of and of β1a or the as with and of cells with and α1S, but of the cells with of the α1S mutants showed β in the ER. the deletion and in and of in this as for both Coexpression of the α1S with the β1a the in cells with β1a and the α1S showed ER of β Thus, the coexpression of or β1a with the α1S the of the the to a tubular/reticular membrane presumably the ER, but this when the β interaction domain in the α1S subunit is of α1S, and in tsA201 in a of the β1a subunit and the α1S with and a specific showed upon coexpression of and the α1S, was colocalized with the α1Ssubunit a and The ER of α1S and were However, when was expressed with or and was not colocalized with the tubular/reticular the α1S subunits in the of the or α1S upon coexpression with specific interactions between the β interaction domain of α1S and β1a the of with the α1S subunit at the ER. However, coexpression of α1S and β1a not in a of α1S within the of the cardiac of the β subunit alone or in combination with the skeletal muscle α1S subunit a different with tsA201 cells with β2a and with the β showed plasma membrane The of the cells was a and the was of The plasma membrane was in where the of the membrane was to the in of the where the membrane was to the plasma membrane of β2a did not when it was with of α1S subunit and However, the of α1S upon coexpression with the ER and in tsA201 cells β2a and α1S showed a of α1S in the of the cells of cells with β2a and α1S a peripheral of α1S The which for the in the ER, as expressed α1S The peripheral α1S was colocalized with the in the plasma membrane. However, the was not throughout the plasma membrane but in in or the plasma membrane. were of and The was of the β2a was in the α1S it was and it between the α1S Thus, α1S is colocalized with β2a, but not throughout the of the of α1S, and β2a in tsA201 in a translocation of α1S the ER to the plasma membrane upon coexpression with β2a was with the α1S. Coexpression of β2a with of the α1S the of the α1S and localized in the ER and a specific interaction between α1S and β2a is involved in the α1S translocation and this interaction requires the intact β interaction domain in α1S. The at which tsA201 cells expressed Ca2+ current with α1S alone or in combination with β1a or β2a was used to the of β subunits to the of Ca2+ channels in the plasma membrane. as of were for of Ca2+ with the a voltage Ca2+ were current at the and were in of cells with α1S and and in of cells with and but in of cells with and the α1S were expressed the β1a subunit, the frequency of was to α1S, of and of The frequency of Ca2+ current upon coexpression of the β1a subunit current α1S. this of was not to the α1S, the showed a with the β1a subunit, but was also with Thus, coexpression of the skeletal muscle β1a subunit current the α1S and the did not of current in the of the β1a subunit. to the of current in cells did not of β1a current The cells with a not in voltage current or current between cells α1S with and coexpression of the cardiac β2a subunit a translocation of the skeletal muscle α1S subunit to the plasma membrane to this current in tsA201 cells. However, to of Ca2+ was as and not different when α1S or was expressed a β subunit were in of cells with β2a the in of cells with β2a Thus, β2a the to the frequency at which skeletal Ca2+ are expressed in tsA201 cells. the of β2a responsible for the translocation of α1S to the plasma membrane is not to β-induced stimulation of Ca2+ current the study used of the α1S subunit of the skeletal muscle l-type Ca2+ channel with and the skeletal and cardiac β subunit isoforms to the and functions of A fusion protein of β1a and the green fluorescent protein and α1S with in the β interaction domain in the cytoplasmic loop between repeats I and II of α1S The of these the of the channel subunits were with and and the of Ca2+ were with The β subunit β1a and β2a, in to with the plasma membrane also in the of the α1S·β and the of The β1a subunit of the skeletal muscle or fusion protein expressed alone in tsA201 was localized diffusely throughout the The was to of alone, and with the plasma membrane or cellular was Thus, the β1a subunit to a specific for the plasma membrane. was different of β2a, which was localized in the plasma membrane when expressed alone in tsA201 cells. with the plasma membrane for and β2a when expressed a α1 subunit in E. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, Campbell K. J. PubMed Scopus Google Scholar), and of was as of β2a E. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). β subunit as and were not localized in the plasma membrane but were distributed throughout the cell when expressed in cells Campbell K. J. PubMed Scopus Google Scholar). Thus, β1a the with and the of β1a a cytoplasmic it not the β1a at in with diffusely distributed membrane or of β1a were in the as as in the when cells were at is with β the and in the Campbell K. J. PubMed Scopus Google Scholar) and with the of the membrane of β2a did not between and E. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). However, the of β1a a cytoplasmic to the ER upon coexpression with α1S β1a is not to cytoplasmic but is for with the β1a and β2a, which are localized in cytoplasmic with the α1S subunit, and this interaction and of channels in the The and the of the skeletal muscle were localized in a tubular/reticular cytoplasmic membrane system, the ER. plasma membrane of α1S was with and were in tsA201 cells with of the α1S The is with the current with the skeletal muscle α1S in as with α1 subunit Thus, a β subunit, of the expressed α1S was in the ER, or was the plasma membrane. β1a was with the the of β1a the of α1S β1a was colocalized with the α1S subunit in the ER. The of β1a upon coexpression with α1S was blocked when the β interaction domain in α1S (α1S-Y366S) or the α1S subunit is for the of β1a with the and this interaction the intact β interaction domain in the cytoplasmic loop between repeats I and II of α1 subunits (12Pragnell M. De Waard M. Mori Y. Tanabe T. Snutch T.P. Campbell K.P. Nature. 1994; 368: 67-70Crossref PubMed Scopus (552) Google Scholar, Waard M. Scott V.E.S. Pragnell M. Campbell K.P. FEBS Lett. 1996; 380: 272-276Crossref PubMed Scopus (82) Google Scholar). a study in this is for the of the β1a subunit but not of the α1S the skeletal muscle U. Glossmann H. Tanabe T. B.E. Proc. Natl. Acad. Sci. U. S. A. Google Scholar). Thus, this interaction is of in the The α1S and β1a with at the ER the of the α1Ssubunit in the the of α1S to the plasma membrane are the formation of the it is in the the of α1S and β1a also in the ER, which a for a of the β subunit in the of α1S to the plasma membrane Campbell K. J. PubMed Scopus Google Scholar). upon coexpression of α1S and Ca2+ β1a is for the of channels in the plasma membrane of tsA201 cells. However, current was not plasma membrane of α1S or Ca2+ a of channels in the plasma membrane is to with The current in to this to the of the in the plasma membrane of the tsA201 cells the of in skeletal muscle where this channel localized with the the of channels in the plasma membrane these channels the with to with β as the channels in the ER, both the is the deletion of the β interaction domain in of both formation and current and was the current was when β1a was with the α1S, which did not with of with to with β1a and current stimulation the of β1a are of and formation but not current stimulation the β interaction domain in the I-II cytoplasmic loop of α1S. β2a expressed alone was localized in the plasma membrane of tsA201 cells. did not upon coexpression with α1S, but the translocation of the α1S subunit the ER to the plasma membrane. The β2a-induced translocation of α1S was with the α1S but not with mutants in which the β interaction domain or a specific interaction of the β2a with the β interaction domain in the I-II cytoplasmic loop of α1S is involved in the α1 subunit in the plasma membrane. However, α1S and β2a were not colocalized in the plasma membrane. β2a distributed throughout the membrane, α1S was localized in of and β2a the of the α1S subunit the plasma membrane but not with α1S when this subunit β2a did not α1S the of β2a to to α1 subunits to of of α1 subunit it β with subunits for the binding in the I-II cytoplasmic loop of Ca2+ channel isoforms K. J. 1995; PubMed Scopus Google Scholar, Waard M. H. Scott V.E.S. Campbell K.P. Nature. PubMed Scopus Google Scholar, E. J. Snutch T.P. Nature. PubMed Scopus Google Scholar). a to β and subunits A β subunit in the plasma membrane the subunits in a interaction β subunits distributed in the β2a is distributed in the plasma membrane and not concentrated in the membrane is with the of β in the plasma membrane of cells. A translocation of the cardiac the subunits and β2a E. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, Campbell K. J. PubMed Scopus Google Scholar, E. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). However, coexpression of these subunit isoforms also in of current with cells α1 subunits the of β2a the skeletal muscle α1S subunit did not to of current The of of a β subunit the binding in the of the β subunit T. A. E. Neuron. 1994; Full Text PDF PubMed Scopus Google Scholar, J. E. J. 1996; PubMed Google Scholar). the cardiac β2a the plasma membrane of α1S. Thus, β isoforms in to the α1 subunit to the plasma membrane as as in to the α1 subunit. the and of current are not α1S current stimulation a specific of the and plasma membrane of a β subunit for of α1S the plasma membrane. the combination of the as to the for the for of the skeletal muscle Ca2+ channel in B.D. G.H. Y. Scheuer T. Catterall W.A. J. PubMed Google Scholar). is with the of a study of skeletal Ca2+ in is coexpression of but not with β1a J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). interactions both membrane and the of in The β1a and β2a, in were both the intact β interaction domain in the cytoplasmic loop between repeats I and II of the α1S subunit. translocation of β1a to the ER in the of β2a, translocation of α1S to the plasma membrane when the β interaction domain was or the β interaction domain in the I-II cytoplasmic loop of α1S is for formation with different β subunit the β is or not where in the cell the the of the β1a subunit to of Ca2+ is to and requires the intact β interaction domain the of α1S and of β1a and the and α1S subunits different of The the β interaction domain in the I-II cytoplasmic loop of α1S of is deletion of the β interaction domain formation with β as as current stimulation upon coexpression of The of of the nine conserved in the β interaction domain to this the to formation the interaction is for the of channels in the membrane. However, α1S membrane β2a, which also interactions with the intact β interaction did not Ca2+ currents. the of a β subunit with α1S the conserved β interaction domain in the I-II cytoplasmic loop not to of Ca2+ currents. interactions with the β interaction domain in the I-II cytoplasmic loop are but not for β-induced current stimulation. the of a domain in α1S for interactions with these the β interaction domain in the I-II cytoplasmic loop of α1S β subunits with (13De Waard M. Scott V.E.S. Pragnell M. Campbell K.P. FEBS Lett. 1996; 380: 272-276Crossref PubMed Scopus (82) Google De Waard M. H. Pragnell M. Campbell K.P. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar), a β interaction domain with β isoforms with a not the of the the system, binding the interaction domain to with the binding the system, of β1a in the this interaction the of the is for the of a binding for the β subunits in the of the subunit E. M. J. E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar) as as for domains in the β subunit are involved in of α1 subunits T. A. E. Neuron. 1994; Full Text PDF PubMed Scopus Google Scholar, J. E. J. 1996; PubMed Google Scholar). the the between interactions of the Ca2+ channel α1S and β subunits and in the of β subunits and the of as as the skeletal muscle α1S subunit are of the of Ca2+ channels β the of interactions are or interaction domains of to S. Froehner and J. Striessnig for of T. Y. and for of and for the of tsA201 cells. also H. for