title: The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation.
abstract: There is molecular diversity in both alpha 1 and beta subunits of voltage-gated Ca2+ channels. Coupling between voltage sensing and pore opening of the C-type alpha 1 (alpha 1c) is improved by the type 2 beta subunit (beta 2), and E-type alpha 1 beta complexes inactivate at different rates depending on the nature of beta. We compared the effects of type 1 and 2 beta subunits on activation of the human E-type alpha 1 (alpha 1E) with the effects they have on inactivation, as seen in Xenopus oocytes. The beta subtypes stimulated activation in similar fashion but affected inactivation differently, and even in opposing directions. beta subunits have a common central core but differ in their N- and C-termini and in a central region. N-terminal chimeras between beta 1 and beta 2 subunits that have opposing effects on inactivation resulted in the reciprocal transfer of their effects. We conclude that regulation of activation and inactivation of alpha 1 by beta are separable events and that the N-terminus of beta is one of the structural determinants important in setting the rate and voltage at which an alpha 1 inactivates.
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: R
authors.initials: R
authors.lastname: Olcese
authors.forename: N
authors.initials: N
authors.lastname: Qin
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.forename: A
authors.initials: A
authors.lastname: Neely
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.forename: E
authors.initials: E
authors.lastname: Stefani
authors.forename: L
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009865:Oocytes; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels