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Pulm Pharmacol Ther. 2013 Oct;26(5):508-9. doi: 10.1016/j.pupt.2013.07.001. Epub 2013 Jul 11.

Regulation of cough and action potentials by voltage-gated Na channels.

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Respiratory Drug Discovery, GlaxoSmithKline, 709 Swedeland Rd, UW 2532, King of Prussia, PA 19406, USA.


The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. Of the nine voltage-gated Na channels, seven are expressed in neurons, of these Nav 1.7, 1.8 and 1.9 are expressed in sensory neurons including vagal sensory neurons that innervate the airways and initiate cough. Nav 1.7 and Nav 1.9 are of particular interest as they represent two extremes in the functional diversity of voltage-gated Na channels. Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.


Antitussive; Cough; Ion channels; Vagal afferent neurons; Voltage-gated Na channels

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