2-Aminoethoxydiphenyl borate stimulates pulmonary C neurons via the activation of TRPV channels

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 288; no. 5; pp. L932 - L941
• Main Authors: Gu, Qihai, Lin, Ruei-Lung, Hu, Hong-Zhen, Zhu, Michael X, Lee, Lu-Yuan
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Animals; Blood Pressure - drug effects; Boron Compounds - pharmacology; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cation Transport Proteins - physiology; Coloring Agents - pharmacology; Heart Rate - drug effects; Ion Channels - physiology; Lung - innervation; Nerve Fibers, Unmyelinated - drug effects; Nerve Fibers, Unmyelinated - physiology; Nodose Ganglion - cytology; Rats; Rats, Sprague-Dawley; Receptors, Drug - physiology; Reflex - drug effects; Respiratory Mechanics - drug effects; Ruthenium Red - pharmacology; TRPV Cation Channels
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00439.2004

1 Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky; and Departments of 2 Physiology and Cell Biology and 3 Neuroscience and Center for Molecular Neurobiology, The Ohio State University, Columbus, Ohio Submitted 23 November 2004 ; accepted in final form 10 January 2005 This study was carried out to determine the effect of 2-aminoethoxydiphenyl borate (2-APB), a common activator of transient receptor potential vanilloid (TRPV) type 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 2-APB 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, 2-APB no longer evoked any of these reflex responses. In open-chest and artificially ventilated rats, 2-APB evoked an abrupt and intense discharge in vagal pulmonary C fibers in a dose-dependent manner. The stimulation of C fibers by 2-APB was attenuated but not abolished by capsazepine, a selective antagonist of the TRPV1, which completely blocked the response to capsaicin in these C fiber afferents. In isolated pulmonary capsaicin-sensitive neurons, 2-APB concentration dependently evoked an inward current that was partially inhibited by capsazepine but almost completely abolished by ruthenium red, an effective blocker of all TRPV channels. In conclusion, 2-APB 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. pulmonary chemoreflex; vagal C fiber; pulmonary sensory neuron; transient receptor potential channels Address for reprint requests and other correspondence: L.-Y. Lee, Dept. of Physiology, Univ. of Kentucky Medical Center, 800 Rose St., Lexington, KY 40536-0298 (E-mail: lylee{at}uky.edu )