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1 Department of Physiology, University of Kentucky, Lexington, KY, USA
2 Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA
3 Department of Neuroscience and Center for Molecular Neurobiology, The Ohio State University, Columbus, OH, USA
* To whom correspondence should be addressed. E-mail: lylee{at}uky.edu.
This study was carried out to determine the effect of 2-aminoethoxydiphenyl borate (2APB), a common activator of transient receptor potential vanilloid (TRPV) types 1, 2 and 3 channels, on cardiorespiratory reflexes, pulmonary C-fiber afferents and isolated pulmonary capsaicin-sensitive neurons. In anesthetized, spontaneously breathing rats, intravenous bolus injection of 2APB elicited the pulmonary chemoreflex responses, characterized by apnea, bradycardia and hypotension. After perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 2APB no longer evoked any of these reflex responses. In open-chest and artificially ventilated rats, 2APB evoked an abrupt and intense discharge in vagal pulmonary C fibers in a dose-dependent manner. The stimulation of C fibers by 2APB was attenuated but not abolished by capsazepine, a selective antagonist of the TRPV1, that completely blocked the response to capsaicin in these C-fiber afferents. In isolated pulmonary capsaicin-sensitive neurons, 2APB concentration-dependently evoked an inward current which is partially inhibited by capsazepine but almost completely abolished by ruthenium red, an effective blocker of all TRPV channels. In conclusion, 2APB evokes a consistent and distinct stimulatory effect on pulmonary C fibers in vivo, and on isolated pulmonary capsaicin-sensitive neurons in vitro. These results establish the functional evidence demonstrating that TRPV1, V2 and V3 channels are expressed on these sensory neurons and their terminals.
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