Spontaneous contractility of human fetal airway smooth muscle.
Physical forces such as fetal breathing and fluid secretion may influence lung development, perhaps by their ability to distend the fetal lung. We found that airway smooth muscle cells in first-trimester human lung tissue and cultured lung tissue explants spontaneously contract. The contractions caused visible movement of intraluminal fluid and distended the distal ends of the epithelial tubules, suggesting that they produced significant changes in intraluminal pressure. Smooth muscle contractility and responses to pharmacologic manipulations were recorded with video microscopy. The interval between contractions ranged from 8 to 135 s (mean +/- SEM, 54 +/- 5 s; n = 20). Smooth muscle contractility was not inhibited by tetrodotoxin or atropine, implying a myogenic rather than neurogenic origin. Because cholinergic nerves modulate adult airway smooth muscle contractility, we asked whether fetal airway smooth muscle cells were regulated by cholinergic agents. The cholinergic agonists acetylcholine and carbachol both increased fetal airway smooth muscle contractility. Contractions were inhibited by the calcium channel blockers CdCl2 and nifedipine, suggesting that an influx of extracellular Ca2+ accompanied airway smooth muscle contractions. Isoproterenol dilated the contractile regions of the epithelial tubules and stopped contractions. Lemakalim, an activator of smooth muscle ATP-sensitive K+ channels, also arrested contractions and relaxed fetal airway smooth muscle. In conclusion, human fetal airway smooth muscle contacts spontaneously and exhibits pharmacologic responsiveness similar to adult airway smooth muscle. We speculate that fetal airway smooth muscle contractions, possibly exerting effects through phasic changes in intraluminal pressure, may be an important physical force contributing to lung development.
McCray
P B
PB
Department of Pediatrics, College of Medicine, University of Iowa, Iowa City.
D002121:Calcium Channel Blockers / Q000494:pharmacology; D018680:Cholinergic Antagonists; D046508:Culture Techniques; D006801:Humans; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000196:embryology / Q000502:physiology*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism; D013696:Temperature; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D010276:Parasympatholytics; D011950:Receptors, Cholinergic; D013779:Tetrodotoxin; D007545:Isoproterenol