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.
Featherstone
Neil C
NC
Division of Child Health, Royal Liverpool Children's Hospital (Alder Hey), School of Biological Sciences, University of Liverpool, Liverpool L69 3BX, UK. N.C.Featherstone@Liverpool.ac.uk
Jesudason
Edwin C
EC
Connell
Marilyn G
MG
Fernig
David G
DG
Wray
Susan
S
Losty
Paul D
PD
Burdyga
Theodor V
TV
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling; D005260:Female; D008168:Lung / Q000196:embryology* / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D020746:Calcium Channels, L-Type