Year of Publication

2008

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Medicine

Department

Physiology

First Advisor

Dr. Lu-Yuan Lee

Abstract

Hyperthermia can occur in lungs and airways during both physiological and pathophysiological conditions. A previous study carried out in our laboratory showed that hyperthermia activates and sensitizes vagal bronchopulmonary Cfiber afferents, whether this effect is through a direct action of hyperthermia on sensory nerves is not known. This dissertation study was aimed to investigate the thermal-sensitivity of pulmonary sensory neurons, and the roles of thermalsensitive transient receptor potential vanilloid (TRPV) channels. Whole-cell patch-clamp recordings of neurons isolated from nodose/jugular ganglia were applied in the study. Results of this study showed that hyperthermia directly activates pulmonary sensory neurons, and this effect is partially mediated through the TRPV subtype 1 (TRPV1) channel as well as other thermal-sensitive TRPV (2–4) channels. In addition, hyperthermia exerts potentiating effects on responses of pulmonary sensory neurons to TRPV1 activators, but not to non- TRPV1 activators. Furthermore, results obtained in the study of TRPV1-null mice revealed that TRPV1 plays a dominant role in mediating the potentiating effect of hyperthermia on pulmonary sensory neurons, but is only partially involved in the direct activation of these sensory neurons by increasing temperature. These results suggested that the thermal-sensitivity of pulmonary sensory neurons is dependent upon the function of the TRPV1 channel, and TRPV1-mediated sensitization of these sensory neurons may contribute to airway hyperreactivity and augmented reflex responses under hyperthermic conditions.

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