title: Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II.
abstract: Calcium entry through voltage-activated Ca2+ channels is important in regulating many cellular functions. Activation of these channels in many cell types results in feedback regulation of channel activity. Mechanisms linking Ca2+ channel activity with its downregulation have been described, but little is known of the events responsible for the enhancement of Ca2+ current that in many cells follows Ca2+ channel activation and an increase in cytoplasmic Ca2+ concentration. Here we investigate how this positive feedback is achieved in single smooth muscle cells. We find that in these cells voltage-activated calcium current is persistently but reversibly enhanced after periods of activation. This persistent enhancement of the Ca2+ current is mediated by activation of calmodulin-dependent protein kinase II because it is blocked when either the rise in cytoplasmic Ca2+ is inhibited or activation of calmodulin-dependent protein kinase II is prevented by specific peptide inhibitors of calcium-calmodulin or calmodulin-dependent protein kinase II itself. This mechanism may be important in different forms of Ca2+ current potentiation, such as those that depend on prior Ca2+ channel activation or are a result of agonist-induced release of Ca2+ from internal stores.
authors.affiliation: Biomedical Imaging Group, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: J G
authors.initials: JG
authors.lastname: McCarron
authors.forename: J G
authors.initials: JG
authors.lastname: McGeown
authors.forename: S
authors.initials: S
authors.lastname: Reardon
authors.forename: M
authors.initials: M
authors.lastname: Ikebe
authors.forename: F S
authors.initials: FS
authors.lastname: Fay
authors.forename: J V
authors.initials: JV
authors.lastname: Walsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002024:Bufo marinus; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*
chemical_list: D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium