title: Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7.
abstract: Synaptotagmin 7 (Syt7) is expressed in cardiac sympathetic nerve terminals where norepinephrine (NE) is released in both Ca(2+)-dependent exocytosis and Ca(2+)-independent norepinephrine transporter (NET)-mediated overflow. The role of Syt7 in the regulation of NE release from cardiac sympathetic nerve terminals is tested by employing a Syt7 knock-in mouse line that expresses a non-functional mutant form of Syt7. In cardiac sympathetic nerve terminals prepared from these Syt7 knock-in mice, the Ca(2+)-dependent component of NE release was diminished. However, these terminals displayed upregulated function of NET (∼130% of controls) and a significant increase in Ca(2+)-independent NE overflow (∼140% of controls), which is greater than the Ca(2+)-dependent component of NE exocytosis occurring in wild-type controls. Consistent with a significant increase in NE overflow, the Syt7 knock-in mice showed significantly higher blood pressures compared to those of littermate wild-type and heterozygous mice. Our results indicate that the lack of functional Syt7 dysregulates NE release from cardiac sympathetic nerve terminals.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Shih
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Lincy
authors.initials: L
authors.lastname: Varghese
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Alice
authors.initials: A
authors.lastname: Bittar
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Chung
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, 77555.
authors.forename: Ok-Ho
authors.initials: OH
authors.lastname: Shin
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis; D055879:Gene Knock-In Techniques; D051379:Mice; D009411:Nerve Endings / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism*; D050857:Synaptotagmins / Q000235:genetics* / Q000378:metabolism
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C494303:Syt7 protein, mouse; D050857:Synaptotagmins; D002118:Calcium; D009638:Norepinephrine
keywords: CARDIAC SYMPATHETIC NERVE TERMINALS; EXOCYTOSIS; NOREPINEPHRINE RELEASE; SYNAPTOTAGMIN 7