Parasympathetic nerves provide the dominant neural control of airway caliber; dysfunction of this pathway may be associated with airway disease. In the parasympathetic nerve pathway, ganglion neurons, located in the airway wall, limit preganglionic signals emanating from the central nervous system. The objectives of this proposal are to develop an understanding of how the intrinsic properties of parasympathetic ganglion neurons serve to filter or integrate excitatory signals, and how the sensory and sympathetic nervous system contribute to this integration. Regulation of guinea pig and human bronchial parasympathetic nerve activity will be investigated using in vitro microelectrode recording techniques.
The first aim will be to determine what membrane properties of guinea pig bronchial ganglion neurons affect the output from these ganglia; included in this aim is the determination of the role muscarinic receptor activation plays in regulating synaptic transmission.
The second aim will be to determine the role sensory nerves and tachykinins play in regulating synaptic transmission in guinea pig bronchial ganglia. The third goal will be to determine the effects of alpha- and beta-adrenergic receptor agonists, as well as the effects of sympathetic nerve stimulation, have on synaptic transmission in guinea bronchial ganglia. Lastly, experiments will be performed on human bronchial ganglion neurons to determine active and passive membrane properties, and the presence and function of muscarinic, tachykinin, and adrenergic receptors using techniques developed with the guinea pig model. In addition, the presence of tachykinin-containing sensory fibers in human ganglia will be indirectly determined by monitoring changes in membrane properties during application of capsaicin, which releases tachykinins from sensory nerve terminals. These studies will provide direct information on the physiological mechanisms that regulate transmission through airway parasympathetic ganglia. Such information may provide important new insights into the role that the nervous system may have in the pathophysiology of airway diseases such as bronchial asthma.
