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

Voltage-gated sodium (Na_v) 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 Na_v channel subunits (Na_v1.7, Na_v1.8, and Na_v1.9) in the aortic baroreceptor neurons and investigated the role of Na_v 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 Na_v1.7 was expressed in A-type (myelinated) and C-type (unmyeli-nated) nodose neurons, but Na_v1.8 and Na_v1.9 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 Na_v channels in nodose neurons. In addition, using the whole-cell patch-clamp technique, we found that Na_v 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, Na_v channel activator (rATX II, 100 nM) signicantly enhanced Na_v 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 Na_v channels are involved in the attenuation of baroreceptor neuron excitability, which subsequently contributes to the impair-ment of baroreex in CHF state.