Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7

Alvin M. Shih, Lincy Varghese, Alice Bittar, Sung Hoon Park, Jin Mo Chung, Ok Ho Shin

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Synaptotagmin 7 (Syt7) is expressed in cardiac sympathetic nerve terminals where norepinephrine (NE) is released in both Ca2+-dependent exocytosis and Ca2+-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 Ca2+-dependent component of NE release was diminished. However, these terminals displayed upregulated function of NET (130% of controls) and a significant increase in Ca2+-independent NE overflow (140% of controls), which is greater than the Ca2+-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. J. Cell. Biochem. 117: 1446-1453, 2016.

Original languageEnglish (US)
Pages (from-to)1446-1453
Number of pages8
JournalJournal of Cellular Biochemistry
Volume117
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • CARDIAC SYMPATHETIC NERVE TERMINALS
  • EXOCYTOSIS
  • NOREPINEPHRINE RELEASE
  • SYNAPTOTAGMIN 7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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