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Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7
Author(s) -
Shih Alvin M.,
Varghese Lincy,
Bittar Alice,
Park SungHoon,
Chung Jin Mo,
Shin OkHo
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25436
Subject(s) - synaptotagmin 1 , norepinephrine , neuroscience , chemistry , psychology , dopamine , biochemistry , synaptic vesicle , vesicle , membrane
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. J. Cell. Biochem. 117: 1446–1453, 2016. © 2015 Wiley Periodicals, Inc.