Abstract
Little is known about the voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. We evaluated the expression of the α subunits of each of the nine NaVs in human, guinea pig, and mouse airway parasympathetic ganglia. We combined this information with a pharmacological analysis of selective NaV blockers on parasympathetic contractions of isolated airway smooth muscle. As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species. Gene expression analysis shown that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea pig and human airway parasympathetic ganglia, where mouse ganglia expressed NaV 1.1, 1.3, and 1.7. Using selective pharmacological blockers supported the gene expression results showing that blocking NaV 1.7 alone can abolish the responses in guinea pig and human bronchi, but not in mouse airways. To block the responses in mouse airways requires that NaV 1.7 along with NaV1.1 and/or NaV 1.3 is blocked. There results may suggest novel indications for NaV1.7 blocking drugs where there is an overactive parasympathetic drive such as in asthma. The data also raise the potential concern of anti-parasympathetic side effects for systemic NaV 1.7 blockers.
- The American Society for Pharmacology and Experimental Therapeutics