title: Role played by NaV 1.7 channels on thin-fiber muscle afferents in transmitting the exercise pressor reflex.
abstract: Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of somatic afferent neurons and are thought to play an important role in the signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than 300 nM. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels in the transmission of muscle afferent input evoking the exercise pressor reflex. We first showed that the exercise pressor reflex, which was evoked by static contraction of the triceps surae muscles, was reversibly attenuated by application of 50 nM TTX, but not 5 nM TTX, to the L4-L5 dorsal roots (control: 21 ± 1 mmHg, TTX: 8 ± 2 mmHg, recovery: 21 ± 3 mmHg; n = 6; P < 0.01). We next found that the peak pressor responses to contraction were significantly attenuated by dorsal root application of 100 nM Ssm6a, a compound that is a selective NaV 1.7 channel inhibitor. Removal of Ssm6a restored the reflex to its control level (control: 19 ± 3 mmHg, Ssm6a: 10 ± 1 mmHg, recovery: 19 ± 4 mmHg; n = 6; P < 0.05). Compound action potentials recorded from the L4 and L5 dorsal roots and evoked by single-pulse stimulation of the sciatic nerve showed that both TTX and Ssm6a attenuated input from group III, as well as group IV afferents. We conclude that NaV 1.7 channels play a role in the thin-fiber muscle afferent pathway evoking the exercise pressor reflex.
authors: Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania.
authors: Audrey J
authors: AJ
authors: Stone
authors: Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania.
authors: Steven W
authors: SW
authors: Copp
authors: Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania mkaufman@hmc.psu.edu.
authors: Marc P
authors: MP
authors: Kaufman
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat
keywords: Ssm6a; TTX-S; group III and IV afferents; neural control of the circulation; rats; voltage-gated sodium channels