title: Promotion and inhibition of L-type Ca2+ channel facilitation by distinct domains of the subunit.
abstract: Ca2+ current potentiation by conditioning depolarization is a general mechanism by which excitable cells can control the level of Ca2+ entry during repetitive depolarizations. Several types of Ca2+ channels are sensitive to conditioning depolarization, however, using clearly distinguishable mechanisms. In the case of L-type Ca2+ channels, prepulse-induced current facilitation can only be recorded when the pore-forming alpha1C subunit is coexpressed with the auxiliary beta1, beta3, or beta4, but not beta2, subunit. These four beta subunits are composed of two conserved domains surrounded by central, N-terminal, and C-terminal variable regions. Using different deleted and chimeric forms of the beta1 and beta2 subunits, we have mapped essential sequences for L-type Ca2+ channel facilitation. A first sequence, located in the second conserved domain of all beta subunits, is responsible for the promotion of current facilitation by the beta subunit. A second sequence of 16 amino acids, located on the N-terminal tail of the beta2 subunit, induces a transferable block of L-type current facilitation. Site-specific mutations reveal the essential inhibitory role played by three positive charges on this segment. The lack of prepulse-induced current facilitation recorded with some truncated forms of the beta2 subunit suggests the existence of an additional inhibitory sequence in the beta2 subunit.
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, CNRS Unité Propre de Recherche 1086, 1919 Route de Mende, BP 5051, F34033 Montpellier, France.
authors.forename: T
authors.initials: T
authors.lastname: Cens
authors.forename: S
authors.initials: S
authors.lastname: Restituito
authors.forename: A
authors.initials: A
authors.lastname: Vallentin
authors.forename: P
authors.initials: P
authors.lastname: Charnet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D002118:Calcium