The long term objective of this project is to assess the neurohumoral control of airway smooth muscle in both the normal cat and in cats with hyperirritable airways induced by ozone inhalation or sensitized by repeated injections of Ascaris extract. Specifically, we will evaluate the transmission of impulses through the tracheal parasympathetic ganglia and the neurohumoral events leading to depolarization and contraction of tracheal smooth muscle. To do this we will record, in vivo, the electrophysiological properties and the spontaneous firing patterns of tracheal ganglion cells during normal breathing and during evoked airway reflexes. We will, by pico spritzer, apply putative transmitters to the ganglia to determine their effect. If any of these agents modify the transmission through the ganglia, we will apply antagonists, to determine if they have an effect on the normal firing of the ganglion cell or upon its response to evoked reflexes. On completion of these studies we will inject the cell with HRP of Lucifer Yellow to identify its morphology and axonal projection and submit it for immunocytochemical and autoradiographic verification of the presence of the physiologically active agent in the immediate vicinity of the identified unit as well as receptors for the agent on the unit. We will also record, simultaneously, tracheal smooth muscle tension and membrane potential in vivo during normal breathing and during evoked airway reflexes. We will, as we have done for tracheal ganglion cells, determine the effect of putative transmitters and their antagonists on the membrane potential and tension of the smooth muscle, and the relationship between them, and identify the presence of the physiologically active agent and its receptors on the identified unit. On completion of these studies, we will evaluate the effect of induced hyperirritability of the airways on transmission through the ganglia and on the electromechanical properties of the tracheal smooth muscle. We believe that the information obtained in the normal and sensitized state of the cat, an animal that has been a major experimental model for the studies of airway reflexes, is essential for our understanding of the neurohumoral control of airways in normal man and in diseased subjects with hyperirritable airways.
| Mitchell, R A; Herbert, D A; Baker, D G et al. (1987) In vivo activity of tracheal parasympathetic ganglion cells innervating tracheal smooth muscle. Brain Res 437:157-60 |
