Regulation of airway smooth muscle cell contractility by Ca2+ signaling and sensitivity.
Airway smooth muscle cell contraction is regulated by changes in intracellular Ca2+ concentration ([Ca2+]i) and the responsiveness of the airway smooth muscle cell to this Ca2+. The mechanism controlling [Ca2+]i primarily involves agonist-induced release of Ca2+ from internal stores to generate Ca2+ oscillations. The extent of contraction correlates with the persistence and frequency of these Ca2+ oscillations. The maintenance of the Ca2+ oscillations requires Ca2+ influx, but membrane depolarization appears to have a minor role in initiating or sustaining contraction. Contraction also requires agonist-induced Ca2+ sensitization, which is mediated mainly by decreases in myosin light-chain phosphatase activity. Although it is not clear if airway hyperresponsiveness associated with asthma results from the specific modulation of these Ca2+-based regulatory mechanisms, bronchodilators relax airways by both attenuating the Ca2+ oscillations and by decreasing the Ca2+ sensitivity.
Sanderson
Michael J
MJ
Department of Physiology University of Massachusetts Medical School Worcester, MA 01655, USA. michael.sanderson@umassmed.edu
Delmotte
Philippe
P
Bai
Yan
Y
Perez-Zogbhi
Jose F
JF
D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology*; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel