Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents
2009
Guo-Fen Qiao, Bai-Yan Li, Yu-Hong Zhou, Yan-Jie Lu, John H. Schild
<p>Persistent tetrodotoxin-resistant (TTX-R) Na<sup>+</sup> (Na<sub>v</sub>1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na<sup>+</sup> although the functional expression of this current was observed in the presence of PGE<sub>2</sub> or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na<sup>+</sup>). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na<sup>+</sup> currents were expressed in 9 out of 38 VANs bathed in 150 mM Na<sup>+</sup>. The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na<sup>+</sup> channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na<sup>+</sup> channels (at -20 mV). This indicates that persistent TTX-R Na<sup>+</sup> channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na<sup>+</sup> currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.</p>
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