The role played by Nav1.8 channels in the somatic pressor chemoreflex

Abstract

Thin fiber muscle afferents (Aδ and C) are supplied by NaV 1.8 channels, whereas thick fiber afferents (spindles) are not. We determined the role played by NaV 1.8 channels on the thin fiber afferents evoking the reflex pressor response to femoral arterial injections of lactic acid (24mM; 0.1mL) and capsaicin (0.1ug) in decerebrated rats with patent or ligated femoral arteries. This was done before and after femoral arterial injection of the A803467 (500μg, 1mg, and 2mg), a NaV 1.8 antagonist. We also recorded the responses of spindles to succinylcholine (200μg) and stretch before and after injecting A803467. In “freely perfused” rats (n=6), A803467 (1mg) significantly reduced the pressor response to lactic acid (16±5 to 4±4ΔmmHg) and capsaicin (47±7 to 26±8ΔmmHg). In “ligated” rats, 1 mg of A803467 significantly reduced the pressor response to lactic acid (32±13 to 3±3ΔmmHg, n=6) but not to capsaicin, which required a dose of 2mg (66±11 to 37±17ΔmmHg, n=4). Surprisingly, we found that A803467 (1mg) reduced the responses of 10 spindles to succinylcholine (34±11 to 4±3 Δ imp/s p=0.04) and stretch (83±17 to 0.4±1 Δ imp/s; p<0.01). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working in part on channels other than NaV 1.8. One possibility is the T type calcium channel, whose blockade with Mibefradil also attenuated the responses of spindles to stretch and succinylcholine.