Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
3
result(s) for
"Jesudason, Susan"
Sort by:
Spontaneous Propagating Calcium Waves Underpin Airway Peristalsis in Embryonic Rat Lung
Prenatal airways from diverse species exhibit spontaneous peristaltic contractions (airway peristalsis). These contractile waves appear coupled to and may function to regulate prenatal lung growth. They are unaffected by atropine or tetrodotoxin but abolished by nifedipine. Nevertheless, the mechanisms by which these contractile waves are generated, regulated, and propagated remain obscure. Using calcium imaging and whole embryonic lung organ culture, we demonstrate for the first time that peristalsis of the embryonic airway is driven by spontaneous, regenerative, temperature-sensitive calcium (Ca2+) waves. These Ca2+ waves propagate between individual airway smooth muscle cells coupled via gap junctions, are likely to be action potential–mediated, and are dependent on not only extracellular calcium entry via L-type voltage-gated channels but also intracellular Ca2+ stores. Thus, if airway peristalsis regulates lung growth, these findings mean that airway smooth muscle Ca2+ waves in turn regulate prenatal lung morphogenesis.
Journal Article
Airway Smooth Muscle Dysfunction Precedes Teratogenic Congenital Diaphragmatic Hernia and May Contribute to Hypoplastic Lung Morphogenesis
Fetal intervention aims to improve lung growth and survival in congenital diaphragmatic hernia (CDH). Airway smooth muscle (ASM) is important in lung development: ASM progenitors produce a key growth factor for lung morphogenesis (fibroblast growth factor 10); ASM contractility is also coupled to growth. ASM hyperreactivity occurs in postnatal CDH and may exacerbate barotrauma via impaired lung compliance. We hypothesize that ASM hyperreactivity and its sequelae are based on an early developmental lesion of ASM activity in hypoplastic lung. Sprague-Dawley rats were fed 100 mg nitrofen on Day 9.5 of pregnancy to induce lung hypoplasia in offspring (controls had vehicle alone). Normal and hypoplastic lung primordia were cultured from Day 13.5 of gestation at 37°C in 5% CO2 and loaded at 54 or 78 h with Ca2+-sensitive indicators: Fluo-4 for confocal imaging and Indo-1 or Fura-2 for photometric measurements of [Ca2+]i. Hypoplastic lung features spontaneous propagating ASM Ca2+ transients with reduced frequency, increased amplitude, and significantly prolonged plateau duration, relative to control lung. Nonetheless, hypoplastic lung exhibits normal requirement for extracellular calcium entry and intracellular calcium release in initiation and regulation of ASM Ca2+ waves. Early ASM dysfunction in lung hypoplasia is apparent as specific anomalies of Ca2+ transients that indicate a problem with plasmalemmal ion channels/action potential generation. Elucidation of such an ASM lesion may allow pharmacologic amelioration not only of ASM hyperreactivity and its sequelae, but also of hypoplastic lung growth itself.
Journal Article