Modulation by tetrodotoxin of action potential discharge in guinea pig vagal tracheal nodose afferent A‐delta cough receptors (660.15)

Abstract

We used the isolated vagally innervated guinea pig trachea/bronchus preparation to characterize the inhibitory effect of tetrodotoxin (TTX) on action potential discharge evoked by electrical (concentric stimulating electrode), and chemical (citric acid) activation of capsaicin‐insensitive nodose A‐delta fibers. We previously described these nerves and bona fide “cough receptors” (Canning et al. J. Physiol, 2004). We have also previously noted at the mRNA, protein, and electrophysiological level that the cell bodies of these nerves express TTX‐sensitive (mainly NaV 1.7) and TTX‐insensitive (both NaV 1.8 and NaV 1.9) channels (J. Physiol. 2008). Here we evaluated 18 nodose fibers with mean CVs of 5.1 ± 0.5 m/s. The voltage threshold of the terminals was 13 ± 1.5 V. The peak following Hz (>95% success for 5s) averaged 30 ± 2 Hz. All fibers responsed to citric acid with an average peak AP discharge of 35 ±6 Hz. Over 95% (17/18) of the fibers were completely silenced with 1 µM TTX. At 0.1 µM, TTX increased the voltage threshold to 24 ± 4 V, reduced the acid response to 10 ± 2 Hz, but had no effect on peak following Hz (studied at 2x V threshold). Jugular neurons project capsaicin‐sensitive A‐delta fibers with CVs the same as the nodose fibers (CV = 6.2 ± 1.4 m/s) and C‐fibers (CV = 0.6 ±0.1 m/s) to the trachea/bronchi. In contrast to nodose A‐delta fibers, only about 50% of jugular A‐delta (5/11) or C‐fibers (5/9) fibers were silenced with 1 µM TTX. These data indicate that although the TTX‐resistant NaVs (1.8 and 1.9) are expressed in nodose tracheal A‐delta cough receptors , they cannot alone support action potential discharge in healthy animals; this is in contrast to the jugular A‐delta and C‐fibers in the trachea/bronchi where TTX‐resistant channels may play a more important role.Grant Funding Source: NIH, Bethesda Maryland, USA