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Post-Ganglionic sympathetic neurons can directly sense raised extracellular Na+ via SCN7a/Nax

Abstract:
The relationship between dietary NaCl intake and high blood pressure is well-established, and occurs primarily through activation of the sympathetic nervous system. Nax, a Na+-sensitive Na+ channel, plays a pivotal role in driving sympathetic excitability, which is thought to originate from central regions controlling neural outflow. We investigated whether post-ganglionic sympathetic neurons from different ganglia innervating cardiac and vasculature tissue can also directly sense extracellular Na+. Using whole-cell patch clamp recordings we demonstrate that sympathetic neurons from three sympathetic ganglia (superior cervical, stellate and superior mesenteric/coeliac) respond to elevated extracellular NaCl concentration. In sympathetic stellate ganglia neurons, we established that the effect of NaCl was dose-dependent and independent of osmolarity, Cl− and membrane Ca2+ flux, and critically dependent on extracellular Na+ concentration. We show that Nax is expressed in sympathetic stellate ganglia neurons at a transcript and protein level using single-cell RNA-sequencing and immunohistochemistry respectively. Additionally, the response to NaCl was prevented by siRNA-mediated knockdown of Nax, but not by inhibition of other membrane Na+ pathways. Together, these results demonstrate that post-ganglionic sympathetic neurons are direct sensors of extracellular Na+ via Nax, which could contribute to sympathetic driven hypertension.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fphys.2022.931094

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Oxford college:
Exeter College
Role:
Author
ORCID:
0000-0001-8453-6133



Publisher:
Frontiers Media
Journal:
Frontiers in Physiology More from this journal
Volume:
13
Article number:
931094
Publication date:
2022-06-17
Acceptance date:
2022-05-24
DOI:
EISSN:
1664-042X
Pmid:
35784866


Language:
English
Keywords:
Pubs id:
1267116
Local pid:
pubs:1267116
Deposit date:
2022-07-13

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