A vagal pulmonary hypoxia sensing pathway regulates breathing
Abstract/Contents
- Abstract
- The carotid body is rapidly activated by hypoxemia and regulates ventilation to maintain blood oxygen levels. Other peripheral hypoxia sensors are not well understood. We molecularly profiled vagal pulmonary sensory neurons by single-cell RNA-sequencing, identified 10 subtypes, and predicted the sensing properties of each subtype based on their mRNA expression profiles. We used genetic strategies and viral tools to characterize a vagal pulmonary sensory neuron subtype (PSN4) that expresses Olfr78, a lactate receptor involved in hypoxia sensing in the carotid body. Individual PSN4 neurons project to multiple sites in the lungs, innervating neuroepithelial bodies, airway smooth muscle, and the alveolar region. They are upstream of neurons in the hypoxia-sensitive circuit of the caudal nucleus of the solitary tract. When optogenetically, or chemogenetically activated, or pharmacologically activated with an Olfr78 agonist, the PSN4 neurons decrease expiratory time, which increases respiratory rate and minute ventilation. They also increase sigh rate. We propose that lactate, produced when airway oxygen levels decline, activates a subset of pulmonary sensory neurons through Olfr78 to increase ventilation and initiate sighs to reinflate collapsed alveoli. We discuss the physiological and disease implications of this second acute hypoxia sensor that regulates ventilation.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Diaz de Arce, Alexander Jordan |
|---|---|
| Degree supervisor | Khosla, Chaitan, 1964- |
| Degree supervisor | Krasnow, Mark, 1956- |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Krasnow, Mark, 1956- |
| Thesis advisor | Chen, Xiaoke |
| Thesis advisor | Kaltschmidt, Julia |
| Degree committee member | Chen, Xiaoke |
| Degree committee member | Kaltschmidt, Julia |
| Associated with | Stanford University, Department of Chemical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Alexander Diaz de Arce. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Alexander Jordan Diaz de Arce
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
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