Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats

Huiyin Tu, Libin Zhang, Thai P. Tran, Robert Leo Muelleman, Yulong Li

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19 Scopus citations

Abstract

Voltage-gated sodium (Nav) channels are responsible for initiation and propagation of action potential in the neurons. To explore the mechanisms of chronic heart failure (CHF)-induced baroreex dysfunction, we measured the expression and current density of Nav channel subunits (Nav1.7, Nav1.8, and Nav1.9) in the aortic baroreceptor neurons and investigated the role of Nav channels in aortic baroreceptor neuron excitability and baroreex sensitivity in sham and CHF rats. CHF was induced by left coronary artery ligation. The development of CHF (6-8 weeks after the coronary ligation) was confirmed by hemodynamic and morphological characteristics. Immunouorescent data indicated that Nav1.7 was expressed in A-type (myelinated) and C-type (unmyeli-nated) nodose neurons, but Nav1.8 and Nav1.9 were expressed only in C-type nodose neurons. Real-time RT-PCR and Western blot data showed that CHF reduced mRNA and protein expression levels of Nav channels in nodose neurons. In addition, using the whole-cell patch-clamp technique, we found that Nav current density and cell excitability of the aortic baroreceptor neurons were lower in CHF rats than that in sham rats. Aortic baroreex sensitivity was blunted in anesthe-tized CHF rats, compared with that in sham rats. Further-more, Nav channel activator (rATX II, 100 nM) signicantly enhanced Nav current density and cell excitability of aortic baroreceptor neurons and improved aortic baroreex sensitivity in CHF rats. These results suggest that reduced expression and activation of the Nav channels are involved in the attenuation of baroreceptor neuron excitability, which subsequently contributes to the impair-ment of baroreex in CHF state.

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Keywords

  • Aortic baroreceptor neuron
  • Baroreex
  • Heart failure
  • Sodium channel

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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