Dysregulation of Norepinephrine Release in the Absence of Functional Synaptotagmin 7

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.