A mathematical analysis of agonist- and KCl-induced Ca(2+) oscillations in mouse airway smooth muscle cells.
Airway hyperresponsiveness is a major characteristic of asthma and is generally ascribed to excessive airway narrowing associated with the contraction of airway smooth muscle cells (ASMCs). ASMC contraction is initiated by a rise in intracellular calcium concentration ([Ca(2+)](i)), observed as oscillatory Ca(2+) waves that can be induced by either agonist or high extracellular K(+) (KCl). In this work, we present a model of oscillatory Ca(2+) waves based on experimental data that incorporate both the inositol trisphosphate receptor and the ryanodine receptor. We then combined this Ca(2+) model and our modified actin-myosin cross-bridge model to investigate the role and contribution of oscillatory Ca(2+) waves to contractile force generation in mouse ASMCs. The model predicts that: 1), the difference in behavior of agonist- and KCl-induced Ca(2+) waves results principally from the fact that the sarcoplasmic reticulum is depleted during agonist-induced oscillations, but is overfilled during KCl-induced oscillations; 2), regardless of the order in which agonist and KCl are added into the cell, the resulting [Ca(2+)](i) oscillations will always be the short-period, agonist-induced-like oscillations; and 3), both the inositol trisphosphate receptor and the ryanodine receptor densities are higher toward one end of the cell. In addition, our results indicate that oscillatory Ca(2+) waves generate less contraction than whole-cell Ca(2+) oscillations induced by the same agonist concentration. This is due to the spatial inhomogeneity of the receptor distributions.
Wang
Inga Y
IY
Department of Mathematics, University of Auckland, Auckland, New Zealand.
Bai
Yan
Y
Sanderson
Michael J
MJ
Sneyd
James
J
D000818:Animals; D001703:Biophysics / Q000379:methods; D002118:Calcium / Q000737:chemistry*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry; D008564:Membrane Potentials; D051379:Mice; D008962:Models, Theoretical; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D009865:Oocytes / Q000378:metabolism; D009991:Oscillometry / Q000379:methods; D011189:Potassium Chloride / Q000737:chemistry*; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry; D013269:Stochastic Processes; D014132:Trachea / Q000166:cytology*; D014981:Xenopus
D053496:Inositol 1,4,5-Trisphosphate Receptors; D019837:Ryanodine Receptor Calcium Release Channel; D011189:Potassium Chloride; D002118:Calcium