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Exclusively in mammals, the diaphragm muscle (DIAm) is the major inspiratory pump, which separates the thoracic and abdominal cavities. With DIAm contraction, a negative intrathoracic and positive abdominal pressure are generated [i.e., transdiaphragmatic pressure (P\n                    <jats:sub>di<\/jats:sub>\n                    )]. During breathing, the DIAm is very active, with a duty cycle (time active vs. inactive) similar to that of the heart. Like the heart, this is a pump that cannot fail! Thus, in controlling breathing, the nervous system must activate DIAm to accomplish pump function while avoiding fatigue. The timing of DIAm activations must also be coordinated with activation of the upper airway muscles (the pipes) to avoid airway occlusion and aspiration and the intercostal and abdominal muscles to appropriately stiffen the body cavities. Similarly, neural control and coordination of the DIAm in nonventilatory behaviors (airway protection, swallowing, vocalization, and voiding) are equally complex, with coordinated activation of the DIAm and abdominal muscles. It is becoming increasingly clear that impaired nonventilatory functions underlie the pathophysiology of a variety of medical conditions. In this review, we will delve into the detailed mechanistic underpinnings of the neural control of the DIAm and the symphonic coordination of its activation during breathing and other behaviors. We will attempt to move the field from considering the DIAm only as an inspiratory pump, emphasizing neural control of airway, intercostal, and abdominal muscles that must be coordinated with DIAm activation.\n                  <\/jats:p>","DOI":"10.1152\/physrev.00043.2024","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T11:30:41Z","timestamp":1752233441000},"page":"2589-2656","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Diaphragm muscle: a pump that can not fail"],"prefix":"10.1152","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-9424","authenticated-orcid":false,"given":"Gary C.","family":"Sieck","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering","place":["United States"]},{"id":[{"id":"https:\/\/ror.org\/02qp3tb03","id-type":"ROR","asserted-by":"publisher"}],"name":"Mayo Clinic","place":["United 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