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Role of NaV 1.7 channels on skeletal muscle afferents in evoking the exercise pressor reflex
Author(s) -
Stone Audrey,
Copp Steven,
Kaufman Marc
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1054.6
Subject(s) - tetrodotoxin , reflex , contraction (grammar) , chemistry , nociception , muscle contraction , anesthesia , hindlimb , stimulation , medicine , endocrinology , anatomy , receptor
Voltage gated sodium channels (NaV) 1.7 can be blocked by tetrodotoxin (TTX) in concentrations of 300nM or less. Moreover, NaV 1.7 channels are highly expressed in sensory neurons and are thought to play a role in inflammatory pain. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels on the axons of thin fiber muscle afferents in evoking the exercise pressor reflex. We first showed that application of 50nM tetrodotoxin to the L3‐L5 dorsal roots attenuated the exercise pressor reflex evoked by statically contracting the hindlimb muscles. The peak pressor responses to static contraction were significantly attenuated by TTX and were restored by replacing the TTX solution with Lactated Ringer's solution (control: 21±1 mmHg, TTX: 8±2 mmHg, restored: 21±3 mmHg; n=6; p<0.01). Likewise, the peak cardioaccelerator responses to contraction were significantly attenuated by TTX (control: 12±3 bpm, TTX: 5±2 bpm, restored: 8±2 bpm; n=6; p<0.05). Similar tensions were developed for each contraction. We next applied the specific NaV 1.7 channel inhibitor, Ssm6a (100nM), to the L3‐L5 dorsal roots to attenuate the reflex. We found that the peak pressor responses to contraction were significantly attenuated by Ssm6a and were restored by replacing the Ssm6a solution with Lactated Ringer's solution (control: 19±3 mmHg, Ssm6a: 10±1 mmHg, recovery: 19±4 mmHg; n=6; p<0.05). In contrast, the peak cardioaccelerator responses to contraction were not attenuated by Ssm6a. Similar tensions were developed for each contraction. We conclude that NaV 1.7 channels, which are TTX‐sensitive, play a role in the afferent pathway evoking the exercise pressor reflex. Funding: NIH AR‐059397