Expression of NaV1.9 channels by muscle afferent neurons (1129.10)

Abstract

Background: The exercise pressor reflex helps regulate cardiovascular responses to exercise. The voltage‐gated sodium channel (Nav) 1.9 has unique properties that could help to generate excessive neuronal activity. We have previously demonstrated the presence of Nav1.9 channels using antibody staining of identified neurons, but were not able to demonstrate functional activity (J Neurophysiol. 108: 2230, 2012). Methods: We voltage‐clamped identified muscle afferent neurons isolated from adult male Sprague Dawley rats and used a high fluoride internal solution to help separate Nav1.9 from Nav1.8. Results: We found a Nav1.9‐like current that activated at voltages 20 mV hyperpolarized to the main Nav1.8 current in 69% of muscle afferent neurons (n=13). This current exhibited significantly slower activation (8 ± 3 ms; n=9) compared with cells that showed only Nav1.8 (4 ± 1 ms; n=4). The Nav current in cells with Nav1.9‐like current inactivated with multiple components compared with a single component inactivation of neurons that showed only Nav1.8. Unexpectedly, the size of the Nav1.9 current declined (ran down) with time during whole‐cell recording, while the Nav1.8 current level appeared to be invariant with time. The current density of the Nav1.9‐like current declined 43% ± 35% (mean ± SD, n=5) over approximately 5 min. We are investigating the role of dialyzable molecules such as ATP in the maintenance of Nav1.9 current. Conclusion: Nav1.9 channels are functionally expressed in muscle afferent neurons. The kinetic properties of Nav1.9 (e.g. slow inactivation) could make this channel an important regulator of muscle afferent activity to exacerbate the exercise pressor reflex.Grant Funding Source: NIH grant AR059397 (KSE) and ATSU BMS grant (TLM)